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Mechanisms of Hormone Carcinogenesis:

Evolution of Views, Role of Mitochondria
  • Jin-Qiang Chen
  • Terry R. Brown
  • James D. Yager
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 630)

Abstract

Cumulative and excessive exposure to estrogens is associated with increased breast cancer risk. The traditional mechanism explaining this association is that estrogens affect the rate of cell division and apoptosis and thus manifest their effect on the risk of breast cancer by affecting the growth of breast epithelial tissues. Highly proliferative cells are susceptible to genetic errors during DNA replication. The action of estrogen metabolites offers a complementary genotoxic pathway mediated by the generation of reactive estrogen quinone metabolites that can form adducts with DNA and generate reactive oxygen species through redox cycling. In this chapter, we discussed a novel mitochondrial pathway mediated by estrogens and their cognate estrogen receptors (ERs) and its potential implications in estrogen-dependent carcinogenesis. Several lines of evidence are presented to show: (1) mitochondrial localization of ERs in human breast cancer cells and other cell types; (2) a functional role for the mitochondrial ERs in regulation of the mitochondrial respiratory chain (MRC) proteins and (3) potential implications of the mitochondrial ER-mediated pathway in stimulation of cell proliferation, inhibition of apoptosis and oxidative damage to mitochondrial DNA. The possible involvement of estrogens and ERs in deregulation of mitochondrial bioenergetics, an important hallmark of cancer cells, is also described. An evolutionary view is presented to suggest that persistent stimulation by estrogens through ER signaling pathways of MRC proteins and energy metabolic pathways leads to the alterations in mitochondrial bioenergetics and contributes to the development of estrogen-related cancers.

Keywords

Breast Cancer Estrogen Receptor Beta Mitochondrial Respiratory Chain Complex Mitochondrial Bioenergetic Breast Cancer Brain Metastasis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Yager JD, Davidson NE. Estrogen carcinogenesis in breast cancer. N Engl J Med 2006; 354(3):270–82.PubMedCrossRefGoogle Scholar
  2. 2.
    Russo J, Hasan Lareef M, Balogh G et al. Estrogen and its metabolites are carcinogenic agents in human breast epithelial cells. J Steroid Biochem Mol Biol 2003; 87(1):1–25.PubMedCrossRefGoogle Scholar
  3. 3.
    Feigelson HS, Henderson BE. Estrogens and breast cancer. Carcinogenesis 1996; 17(11):2279–84.PubMedCrossRefGoogle Scholar
  4. 4.
    Okobia MN, Bunker CH. Estrogen metabolism and breast cancer risk—a review. Afr J Reprod Health 2006; 10(1):13–25.PubMedCrossRefGoogle Scholar
  5. 5.
    Tsai MJ, O’Malley BW. Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Annu Rev Biochem 1994; 63451–86.Google Scholar
  6. 6.
    Pettersson K, Delaunay F, Gustafsson JA. Estrogen receptor beta acts as a dominant regulator of estrogen signaling. Oncogene 2000; 19(43):4970–78.PubMedCrossRefGoogle Scholar
  7. 7.
    Song RX, Barnes CJ, Zhang Z et al. The role of Shc and insulin-like growth factor 1 receptor in mediating the translocation of estrogen receptor alpha to the plasma membrane. Proc Natl Acad Sci USA 2004; 101(7):2076–81.PubMedCrossRefGoogle Scholar
  8. 8.
    Levin ER. Integration of the extranuclear and nuclear actions of estrogen. Mol Endocrinol 2005; 19(8):1951–59.PubMedCrossRefGoogle Scholar
  9. 9.
    Chen JQ, Eshete M, Alworth WL et al. Binding of MCF-7 cell mitochondrial proteins and recombinant human estrogen receptors alpha and beta to human mitochondrial DNA estrogen response elements. J Cell Biochem 2004; 93(2):358–73.PubMedCrossRefGoogle Scholar
  10. 10.
    Chen JQ, Yager JD. Estrogen’s effects on mitochondrial gene expression: mechanisms and potential contributions to estrogen carcinogenesis. Ann N Y Acad Sci 2004; 1028258–72.Google Scholar
  11. 11.
    Chen JQ, Delannoy M, Cooke C et al. Mitochondrial localization of ERalpha and ERbeta in human MCF7 cells. Am J Physiol Endocrinol Metab 2004; 286(6):E1011–22.PubMedCrossRefGoogle Scholar
  12. 12.
    Pedram A, Razandi M, Wallace DC et al. Functional estrogen receptors in the mitochondria of breast cancer cells. Mol Biol Cell 2006; 17(5):2125–37.PubMedCrossRefGoogle Scholar
  13. 13.
    Green DR, Reed JC, Mitochondria and apoptosis. Science 1998; 281(5381):1309–312.PubMedCrossRefGoogle Scholar
  14. 14.
    Bossy-Wetzel E, Green DR, Apoptosis: checkpoint at the mitochondrial frontier. Mutat Res 1999; 434(3):243–51.PubMedGoogle Scholar
  15. 15.
    Kelly DP, Scarpulla RC. Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev 2004; 18(4):357–68.PubMedCrossRefGoogle Scholar
  16. 16.
    Clayton DA. Transcription and replication of mitochondrial DNA. Hum Reprod 2000; 15 Suppl 211–17.Google Scholar
  17. 17.
    Clayton DA. Replication and transcription of vertebrate mitochondrial DNA. Annu Rev Cell Biol 1991; 7453–478.Google Scholar
  18. 18.
    Psarra AM, Solakidi S, Sekeris CE. The mitochondrion as a primary site of action of steroid and thyroid hormones: presence and action of steroid and thyroid hormone receptors in mitochondria of animal cells. Mol Cell Endocrinol 2006; 246(1–2):21–33.PubMedCrossRefGoogle Scholar
  19. 19.
    Mansour AM, Nass S. In vivo cortisol action on RNA synthesis in rat liver nuclei and mitochondria. Nature 1970; 228(272):665–67.PubMedCrossRefGoogle Scholar
  20. 20.
    Yu FL, Feigelson P. A comparative study of RNA synthesis in rat hepatic nuclei and mitochondria under the influence of cortisone of cortisone. Biochim Biophys Acta 1970; 213(1):134–141.PubMedGoogle Scholar
  21. 21.
    Cornwall GA, Orgebin-Crist MC, Hann SR. Differential expression of the mouse mitochondrial genes and the mitochondrial RNA-processing endoribonuclease RNA by androgens. Mol Endocrinol 1992; 6(7):1032–42.PubMedCrossRefGoogle Scholar
  22. 22.
    Demonacos CV, Karayanni N, Hatzoglou E et al. Mitochondrial genes as sites of primary action of steroid hormones. Steroids 1996; 61(4):226–32.PubMedCrossRefGoogle Scholar
  23. 23.
    Demonacos C, Djordjevic-Markovic R, Tsawdaroglou N et al. The mitochondrion as a primary site of action of glucocorticoids: the interaction of the glucocorticoid receptor with mitochondrial DNA sequences showing partial similarity to the nuclear glucocorticoid responsive elements. J Steroid Biochem Mol Biol 1995; 55(1):43–55.PubMedCrossRefGoogle Scholar
  24. 24.
    Scheller K, Sekeris CE Krohne G et al. Localization of glucocorticoid hormone receptors in mitochondria of human cells. Eur J Cell Biol 2000; 79(5):299–307.PubMedCrossRefGoogle Scholar
  25. 25.
    Scheller K, Sekeris CE. The effects of steroid hormones on the transcription of genes encoding enzymes of oxidative phosphorylation. Exp Physiol 2003; 88(1):129–40.PubMedCrossRefGoogle Scholar
  26. 26.
    Scheller K, Seibel P, Sekeris CE. Glucocorticoid and thyroid hormone receptors in mitochondria of animal cells. Int Rev Cytol 2003; 2221–61.Google Scholar
  27. 27.
    Moutsatsou P, Psarra AM, Tsiapara A et al. Localization of the glucocorticoid receptor in rat brain mitochondria. Arch Biochem Biophys 2001; 386(1):69–78.PubMedCrossRefGoogle Scholar
  28. 28.
    Kessler MA, Lamm L, Jarnagin K et al. 1,25-Dihydroxyvitamin D3-stimulated mRNAs in rat small intestine. Arch Biochem Biophys 1986; 251(2):403–12.PubMedCrossRefGoogle Scholar
  29. 29.
    Casas F, Rochard P, Rodier A et al. A variant form of the nuclear triiodothyronine receptor c-ErbAalpha1 plays a direct role in regulation of mitochondrial RNA synthesis. Mol Cell Biol 1999; 19(12):7913–24.PubMedGoogle Scholar
  30. 30.
    Wrutniak-Cabello C, Casas F, Cabello G. Thyroid hormone action in mitochondria. J Mol Endocrinol 2001; 26(1):67–77.PubMedCrossRefGoogle Scholar
  31. 31.
    Enriquez JA, Fernandez-Silva P, Garrido-Perez N et al. Direct regulation of mitochondrial RNA synthesis by thyroid hormone. Mol Cell Biol 1999; 19(1):656–70.Google Scholar
  32. 32.
    Chen JQ, Yager JD, Russo J. Regulation of mitochondrial respiratory chain structure and function by estrogens/estrogen receptors and potential physiological/pathophysiological implications. Biochim Biophys Acta 2005; 1746(1):1–17.PubMedCrossRefGoogle Scholar
  33. 33.
    Casas F, Domenjoud L, Rochard P et al. A 45 kDa protein related to PPAR gamma2, induced by peroxisome proliferators, is located in the mitochondrial matrix. FEBS Lett 2000; 478(1–2):4–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Psarra AM, Bochaton-Piallat ML, Gabbiani G et al. Mitochondrial localization of glucocortocoid receptor in glial (Muller) cells in the salamander retina. Glia 2003; 41(1):38–49.PubMedCrossRefGoogle Scholar
  35. 35.
    Morrish F, Buroker NE, Ge M et al. Thyroid hormone receptor isoforms localize to cardiac mitochondrial matrix with potential for binding to receptor elements on mtDNA. Mitochondrion 2006; 6(3):143–48.PubMedCrossRefGoogle Scholar
  36. 36.
    Wrutniak C, Cassar-Malek I, Marchal S et al. A 43-kDa protein related to c-Erb A alpha 1 is located in the mitochondrial matrix of rat liver. J Biol Chem 1995; 270(27):16347–54.PubMedCrossRefGoogle Scholar
  37. 37.
    Yang SH, Liu R, Perez EJ et al. Mitochondrial localization of estrogen receptor beta. Proc Natl Acad Sci USA 2004; 101(12):4130–35.PubMedCrossRefGoogle Scholar
  38. 38.
    Monje P, Boland R. Subcellular distribution of native estrogen receptor alpha and beta isoforms in rabbit uterus and ovary. J Cell Biochem 2001; 82(3):467–79.PubMedCrossRefGoogle Scholar
  39. 39.
    Solakidi S, Psarra AM, Nikolaropoulos S et al. Estrogen receptors {alpha} and ta (ER{alpha} ERta) and androgen receptor (AR) in human sperm: localization of ERta and AR in mitochondria of the midpiece. Hum Reprod 2005; 20(12):3481–87.PubMedCrossRefGoogle Scholar
  40. 40.
    Ioannou IM, Tsawdaroglou N, Sekeris CE. Presence of glucocorticoid responsive elements in the mitochondrial genome. Anticancer Res 1988; 8(6):1405–09.PubMedGoogle Scholar
  41. 41.
    Demonacos C, Djordjevic-Markovic R, Tsawdaroglou N et al. The mitochondrion as a primary site of action of glucocorticoids: the interaction of the glucocorticoid receptor with mitochondrial DNA sequences showing partial similarity to the nuclear glucocorticoid responsive elements. J Steroid Biochem Mol Biol 1995; 55(1):43–55.PubMedCrossRefGoogle Scholar
  42. 42.
    Demonacos C, Tsawdaroglou NC, Djordjevic-Markovic R et al. Import of the glucocorticoid receptor into rat liver mitochondria in vivo and in vitro. J Steroid Biochem Mol Biol 1993; 46(3):401–43.PubMedCrossRefGoogle Scholar
  43. 43.
    Demonacos CV, Karayanni N, Hatzoglou E et al. Mitochondrial genes as sites of primary action of steroid hormones. Steroids 1996; 61(4):226–32.PubMedCrossRefGoogle Scholar
  44. 44.
    Tsiriyotis C, Spandidos DA, Sekeris CE. The mitochondrion as a primary site of action of glucocorticoids: mitochondrial nucleotide sequences, showing similarity to hormone response elements, confer dexamethasone inducibility to chimaeric genes transfected in LATK-cells. Biochem Biophys Res Commun 1997; 235(2):349–54.PubMedCrossRefGoogle Scholar
  45. 45.
    Sekeris CE. The mitochondrial genome: a possible primary site of action of steroid hormones. In vivo 1990; 4(5):317–20.PubMedGoogle Scholar
  46. 46.
    Casas F, Rochard P, Rodier A et al. A variant form of the nuclear triiodothyronine receptor c-ErbAalpha1 plays a direct role in regulation of mitochondrial RNA synthesis. Mol Cell Biol 1999; 19(12):7913–24.PubMedGoogle Scholar
  47. 47.
    Enriquez JA, Fernandez-Silva P, Garrido-Perez N et al. Direct regulation of mitochondrial RNA synthesis by thyroid hormone. Mol Cell Biol 1999; 19(1):657–70.PubMedGoogle Scholar
  48. 48.
    Wrutniak C, Cassar-Malek I, Marchal S et al. A 43-kDa protein related to c-Erb A alpha 1 is located in the mitochondrial matrix of rat liver. J Biol Chem 1995; 270(27):16347–54.PubMedCrossRefGoogle Scholar
  49. 49.
    Sekeris CE. The mitochondrial genome: a possible primary site of action of steroid hormones. In vivo 1990; 4(5):317–20.PubMedGoogle Scholar
  50. 50.
    Sionov RV, Kfir S, Zafrir E et al. Glucocorticoid-induced apoptosis revisited: a novel role for glucocorticoid receptor translocation to the mitochondria. Cell Cycle 2006; 5(10):1017–26.PubMedGoogle Scholar
  51. 51.
    Sionov RV, Cohen O, Kfir S et al. Role of mitochondrial glucocorticoid receptor in glucocorticoid-induced apoptosis. J Exp Med 2006; 203(1):189–201.PubMedCrossRefGoogle Scholar
  52. 52.
    Bassett JH, Harvey CB, Williams GR. Mechanisms of thyroid hormone receptor-specific nuclear and extra nuclear actions. Mol Cell Endocrinol 2003; 213(1):1–11.PubMedCrossRefGoogle Scholar
  53. 53.
    Psarra AM, Solakidi S, Sekeris CE. The mitochondrion as a primary site of action of regulatory agents involved in neuroimmunomodulation. Ann N Y Acad Sci 2006; 1088:12–22.PubMedCrossRefGoogle Scholar
  54. 54.
    Monje P, Zanello S, Holick M et al. Differential cellular localization of estrogen receptor alpha in uterine and mammary cells. Mol Cell Endocrinol 2001; 181(1–2):117–29.PubMedCrossRefGoogle Scholar
  55. 55.
    Chen JQ, Eshete M, Alworth WL et al. Binding of MCF-7 cell mitochondrial proteins and recombinant human estrogen receptors alpha and beta to human mitochondrial dna estrogen response elements. J Cell Biochem 2004; 93(2):358.PubMedCrossRefGoogle Scholar
  56. 56.
    Pedram A, Razandi M, Wallace DC et al. Functional Estrogen Receptors in the Mitochondria of Breast Cancer Cells. Mol Biol Cell 2006; 17(5):2125–37.PubMedCrossRefGoogle Scholar
  57. 57.
    Solakidi S, Psarra AM, Sekeris CE. Differential subcellular distribution of estrogen receptor isoforms: localization of ERalpha in the nucleoli and ERbeta in the mitochondria of human osteosarcoma SaOS-2 and hepatocarcinoma HepG2 cell lines. Biochim Biophys Acta 2005; 1745(3):382–92.PubMedCrossRefGoogle Scholar
  58. 58.
    Cammarata PR, Chu S, Moor A et al. Subcellular distribution of native estrogen receptor alpha and beta subtypes in cultured human lens epithelial cells. Exp Eye Res 2004; 78(4):861–71.PubMedCrossRefGoogle Scholar
  59. 59.
    Cammarata PR, Flynn J, Gottipati S et al. Differential expression and comparative subcellular localization of estrogen receptor beta isoforms in virally transformed and normal cultured human lens epithelial cells. Exp Eye Res 2005; 81(2):165–75.PubMedCrossRefGoogle Scholar
  60. 60.
    Jonsson D, Nilsson J, Odenlund M et al. Demonstration of mitochondrial oestrogen receptor beta and oestrogen-induced attenuation of cytochrome c oxidase subunit I expression in human periodontal ligament cells. Arch Oral Biol 2007; 52(7):669–76.PubMedCrossRefGoogle Scholar
  61. 61.
    Milner TA, Ayoola K, Drake CT et al. Ultrastructural localization of estrogen receptor beta immunoreactivity in the rat hippocampal formation. J Comp Neurol 2005; 491(2):81–95.PubMedCrossRefGoogle Scholar
  62. 62.
    Stirone C, Duckles SP, Krause DN et al. Estrogen increases mitochondrial efficiency and reduces oxidative stress in cerebral blood vessels. Mol Pharmacol 2005; 68(4):959–65.PubMedCrossRefGoogle Scholar
  63. 63.
    Van Itallie CM, Dannies PS. Estrogen induces accumulation of the mitochondrial ribonucleic acid for subunit II of cytochrome oxidase in pituitary tumor cells. Mol Endocrinol 1988; 2(4):332–37.PubMedCrossRefGoogle Scholar
  64. 64.
    Bettini E, Maggi A. Estrogen induction of cytochrome c oxidase subunit III in rat hippocampus. J Neurochem 1992; 58(5):1923–29.PubMedCrossRefGoogle Scholar
  65. 65.
    Chen J, Schwartz DA, Young TA et al. Identification of genes whose expression is altered during mitosuppression in livers of ethinyl estradiol-treated female rats. Carcinogenesis 1996; 17(12):2783–86.PubMedCrossRefGoogle Scholar
  66. 66.
    Chen J, Gokhale M, Li Y et al. Enhanced levels of several mitochondrial mRNA transcripts and mitochondrial superoxide production during ethinyl estradiol-induced hepatocarcinogenesis and after estrogen treatment of HepG2 cells. Carcinogenesis 1998; 19(12):2187–93.PubMedCrossRefGoogle Scholar
  67. 67.
    Chen J, Delannoy M, Odwin S et al. Enhanced mitochondrial gene transcript, ATP, bcl-2 protein levels and altered glutathione distribution in ethinyl estradiol-treated cultured female rat hepatocytes. Toxicol Sci 2003; 75(2):271–78.PubMedCrossRefGoogle Scholar
  68. 68.
    Hsieh YC, Yu HP, Suzuki T et al. Upregulation of mitochondrial respiratory complex IV by estrogen receptor-beta is critical for inhibiting mitochondrial apoptotic signaling and restoring cardiac functions following trauma-hemorrhage. J Mol Cell Cardiol 2006; 41(3):511–21.PubMedCrossRefGoogle Scholar
  69. 69.
    Stirone C, Duckles SP, Krause DN et al. Estrogen increases mitochondrial efficiency and reduces oxidative stress in cerebral blood vessels. Mol Pharmacol 2005; 68(4):959–65.PubMedCrossRefGoogle Scholar
  70. 70.
    Hatzoglou E, Sekeris CE. The detection of nucleotide sequences with strong similarity to hormone responsive elements in the genome of eubacteria and archaebacteria and their possible relation to similar sequences present in the mitochondrial genome. J Theor Biol 1997; 184(3):339–44.PubMedCrossRefGoogle Scholar
  71. 71.
    Grivell LA. Nucleo-mitochondrial interactions in mitochondrial gene expression. Crit Rev Biochem Mol Biol 1995; 30(2):121–64.PubMedCrossRefGoogle Scholar
  72. 72.
    Garesse R, Vallejo CG. Animal mitochondrial biogenesis and function: a regulatory cross-talk between two genomes. Gene 2001; 263(1–2):1–16.PubMedCrossRefGoogle Scholar
  73. 73.
    Roberts, Szego CM. The influence of steroids on uterine respiration and glycolysis. J Biol Chem 1953; 201(1):21–30.PubMedGoogle Scholar
  74. 74.
    Chen J, Li Y, Lavigne JA et al. Increased mitochondrial superoxide production in rat liver mitochondria, rat hepatocytes and HepG2 cells following ethinyl estradiol treatment. Toxicol Sci 1999; 51(2):224–35.PubMedCrossRefGoogle Scholar
  75. 75.
    Watanabe T, Inoue S, Hiroi H et al. Isolation of estrogen-responsive genes with a CpG island library. Mol Cell Biol 1998; 18(1):442–49.PubMedGoogle Scholar
  76. 76.
    Thompson CJ, Tam NN, Joyce JM et al. Gene expression profiling of testosterone and estradiol-17 beta-induced prostatic dysplasia in Noble rats and response to the antiestrogen ICI 182,780. Endocrinology 2002; 143(6):2093–105.PubMedCrossRefGoogle Scholar
  77. 77.
    Weisz A, Basile W, Scafoglio C et al. Molecular identification of ERalpha-positive breast cancer cells by the expression profile of an intrinsic set of estrogen regulated genes. J Cell Physiol 2004; 200(3):440–50.PubMedCrossRefGoogle Scholar
  78. 78.
    O’Lone R, Knorr K, Jaffe IZ et al. Estrogen Receptors {alpha} and ta Mediate Distinct Pathways of Vascular Gene Expression, Including Genes Involved in Mitochondrial Electron Transport and Generation of Reactive Oxygen Species. Mol Endocrinol 2007 [Epub ahead of print].Google Scholar
  79. 79.
    Huss JM, Torra IP, Staels B et al. Estrogen-related receptor alpha directs peroxisome proliferator-activated receptor alpha signaling in the transcriptional control of energy metabolism in cardiac and skeletal muscle. Mol Cell Biol 2004; 24(20):9079–91.PubMedCrossRefGoogle Scholar
  80. 80.
    Huss JM, Kelly DP. Nuclear receptor signaling and cardiac energetics. Circ Res 2004; 95(6):568–78.PubMedCrossRefGoogle Scholar
  81. 81.
    Zhai P, Eurell TE, Cooke PS et al. Myocardial ischemia-reperfusion injury in estrogen receptor-alpha knockout and wild-type mice. Am J Physiol Heart Circ Physiol 2000; 278(5):H1640–47.PubMedGoogle Scholar
  82. 82.
    Rodriguez-Cuenca S, Pujol E, Justo R et al. Sex-dependent thermogenesis, differences in mitochondrial morphology and function and adrenergic response in brown adipose tissue. J Biol Chem 2002; 277(45):42958–63.PubMedCrossRefGoogle Scholar
  83. 83.
    Justo R, Frontera M, Pujol E et al. Gender-related differences in morphology and thermogenic capacity of brown adipose tissue mitochondrial subpopulations. Life Sci 2005; 76(10):1147–58.PubMedCrossRefGoogle Scholar
  84. 84.
    Degani H, Shaer A, Victor TA et al. Estrogen-induced changes in high-energy phosphate metabolism in rat uterus: 31P NMR studies. Biochemistry 1984; 23(12):2572–77.PubMedCrossRefGoogle Scholar
  85. 85.
    Chen J, Gokhale M, Schofield B et al. Inhibition of TGF-beta-induced apoptosis by ethinyl estradiol in cultured, precision cut rat liver slices and hepatocytes. Carcinogenesis 2000; 21(6):1205–11.PubMedCrossRefGoogle Scholar
  86. 86.
    Justo R, Boada J, Frontera M et al. Gender dimorphism in rat liver mitochondrial oxidative metabolism and biogenesis. Am J Physiol Cell Physiol 2005; 289(2):C372–78.PubMedCrossRefGoogle Scholar
  87. 87.
    Doan VD, Gagnon S, Joseph V. Prenatal blockade of estradiol synthesis impairs respiratory and metabolic responses to hypoxia in newborn and adult rats. Am J Physiol Regul Integr Comp Physiol 2004; 287(3):R612–18.PubMedGoogle Scholar
  88. 88.
    Papa S. Mitochondrial oxidative phosphorylation changes in the life span. Molecular aspects and physiopathological implications. Biochim Biophys Acta 1996; 127(2):87–105.Google Scholar
  89. 89.
    Boyer PD. The ATP synthase—a splendid molecular machine. Annu Rev Biochem 1997; 66717–49.Google Scholar
  90. 90.
    Brodie A, Lu Q, Nakamura J. Aromatase in the normal breast and breast cancer. J Steroid Biochem Mol Biol 1997; 61(3–6):281–86.PubMedCrossRefGoogle Scholar
  91. 91.
    Santen RJ, Santner SJ, Pauley RJ et al. Estrogen production via the aromatase enzyme in breast carcinoma: which cell type is responsible? J Steroid Biochem Mol Biol 1997; 61(3–6):267–71.PubMedCrossRefGoogle Scholar
  92. 92.
    Chen S, Itoh T, Wu K. et al. Transcriptional regulation of aromatase expression in human breast tissue. J Steroid Biochem Mol Biol 2002; 83(1–5):93–99.PubMedCrossRefGoogle Scholar
  93. 93.
    Yue W, Santen RJ, Wang JP et al. Aromatase within the breast. Endocr Relat Cancer 1999; 6(2):157–64.PubMedCrossRefGoogle Scholar
  94. 94.
    Kim H, You S, Kim IJ et al. Increased mitochondrial-encoded gene transcription in immortal DF-1 cells. Exp Cell Res 2001; 265(2):339–47.PubMedCrossRefGoogle Scholar
  95. 95.
    Dong X, Ghoshal K, Majumder S et al. Mitochondrial transcription factor A and its downstream targets are up-regulated in a rat hepatoma. J Biol Chem 2002; 277(45):43309–18.PubMedCrossRefGoogle Scholar
  96. 96.
    Wilden PA, Agazie YM, Kaufman R et al. ATP-stimulated smooth muscle cell proliferation requires independent ERK and PI3K signaling pathways. Am J Physiol 1998; 275(4 Pt 2):H1209–15.PubMedGoogle Scholar
  97. 97.
    Shen J, Halenda SP, Sturek M et al. Cell-signaling evidence for adenosine stimulation of coronary smooth muscle proliferation via the A1 adenosine receptor. Circ Res 2005; 97(6):574–82.PubMedCrossRefGoogle Scholar
  98. 98.
    Shen J, Halenda SP, Sturek M et al. Novel mitogenic effect of adenosine on coronary artery smooth muscle cells: role for the A1 adenosine receptor. Circ Res 2005; 96(9):982–90.PubMedCrossRefGoogle Scholar
  99. 99.
    Heo JS, Han HJ. ATP stimulates mouse embryonic stem cell proliferation via protein kinase C, phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase signaling pathways. Stem Cells 2006; 24(12):2637–48.PubMedCrossRefGoogle Scholar
  100. 100.
    Yu SM, Chen SF, Lau YT et al. Mechanism of extracellular ATP-induced proliferation of vascular smooth muscle cells. Mol Pharmacol 1996; 50(4):1000–09.PubMedGoogle Scholar
  101. 101.
    Wagstaff SC, Bowler WB, Gallagher JA et al. Extracellular ATP activates multiple signalling pathways and potentiates growth factor-induced c-fos gene expression in MCF-7 breast cancer cells. Carcinogenesis 2000; 21(12):2175–81.PubMedCrossRefGoogle Scholar
  102. 102.
    Schafer R, Sedehizade F, Welte T et al. ATP-and UTP-activated P2Y receptors differently regulate proliferation of human lung epithelial tumor cells. Am J Physiol Lung Cell Mol Physiol 2003; 285(2): L376–85.PubMedGoogle Scholar
  103. 103.
    Felty Q, Roy D. Mitochondrial signals to nucleus regulate estrogen-induced cell growth. Med Hypotheses 2005; 64(1):133–41.PubMedCrossRefGoogle Scholar
  104. 104.
    Felty Q, Roy D. Estrogen, mitochondria and growth of cancer and noncancer cells. J Carcinog 2005; 4(1):1.PubMedCrossRefGoogle Scholar
  105. 105.
    Felty Q, Xiong WC, Sun D et al. Estrogen-induced mitochondrial reactive oxygen species as signal-transducing messengers. Biochemistry 2005; 44(18):6900–09.PubMedCrossRefGoogle Scholar
  106. 106.
    Felty Q, Singh KP, Roy D. Estrogen-induced G(1)/S transition of G(0)-arrested estrogen-dependent breast cancer cells is regulated by mitochondrial oxidant signaling. Oncogene 2005; 24(31):4883–93.PubMedCrossRefGoogle Scholar
  107. 107.
    Karpuzoglu E, Fenaux JB, Phillips RA et al. Estrogen up-regulates inducible nitric oxide synthase, nitric oxide and cyclooxygenase-2 in splenocytes activated with T-cell stimulants: role of interferon-gamma. Endocrinology 2006; 147(2):662–71.PubMedCrossRefGoogle Scholar
  108. 108.
    Richard SM, Bailliet G, Paez GL et al. Nuclear and mitochondrial genome instability in human breast cancer. Cancer Res 2000; 60(15):4231–37.PubMedGoogle Scholar
  109. 109.
    Bianchi NO, Bianchi MS, Richard SM. Mitochondrial genome instability in human cancers. Mutat Res 2001; 488(1):9–23.PubMedCrossRefGoogle Scholar
  110. 110.
    Parrella P, Xiao Y, Fliss M et al. Detection of mitochondrial DNA mutations in primary breast cancer and fine-needle aspirates. Cancer Res 2001; 61(20):7623–26.PubMedGoogle Scholar
  111. 111.
    Tan DJ, Bai RK, Wong LJ. Comprehensive scanning of somatic mitochondrial DNA mutations in breast cancer. Cancer Res 2002; 62(4):972–76.PubMedGoogle Scholar
  112. 112.
    Canter JA, Kallianpur AR, Parl FF et al. Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African-American women. Cancer Res 2005; 65(17):8028–33.PubMedGoogle Scholar
  113. 113.
    Mims MP, Hayes TG, Zheng S et al. Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African-American women. Cancer Res 2006; 66(3):1880; author reply 1880–81.PubMedCrossRefGoogle Scholar
  114. 114.
    Habano W, Sugai T, Nakamura S et al. Reduced expression and loss of heterozygosity of the SDHD gene in colorectal and gastric cancer. Oncol Rep 2003; 10(5):1375–80.PubMedGoogle Scholar
  115. 115.
    Neumann HP, Pawlu C, Peczkowska M et al. Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations. Jama 2004; 292(8):943–51.PubMedCrossRefGoogle Scholar
  116. 116.
    Baysal BE, Ferrell RE, Willett-Brozick JE et al. Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 2000; 287(5454):848–51.PubMedCrossRefGoogle Scholar
  117. 117.
    Petros JA, Baumann AK, Ruiz-Pesini E et al. mtDNA mutations increase tumorigenicity in prostate cancer. Proc Natl Acad Sci USA 2005; 102(3):719–24.PubMedCrossRefGoogle Scholar
  118. 118.
    Shidara Y, Yamagata K, Kanamori T et al. Positive contribution of pathogenic mutations in the mitochondrial genome to the promotion of cancer by prevention from apoptosis. Cancer Res 2005; 65(5):1655–63.PubMedCrossRefGoogle Scholar
  119. 119.
    Amuthan G, Biswas G, Zhang SY et al. Mitochondria-to-nucleus stress signaling induces phenotypic changes, tumor progression and cell invasion. EMBO J 2001; 20(8):1910–20.PubMedCrossRefGoogle Scholar
  120. 120.
    Gao N, Ding M, Zheng JZ et al. Vanadate-induced expression of hypoxia-inducible factor 1 alpha and vascular endothelial growth factor through phosphatidylinositol 3-kinase/Akt pathway and reactive oxygen species. J Biol Chem 2002; 277(35):31963–71.PubMedCrossRefGoogle Scholar
  121. 121.
    Perillo B, Sasso A, Abbondaza C et al. 17beta-estradiol inhibits apoptosis in MCF-7 cells, inducing bcl-2 expression via two estrogen-responsive elements present in the coding sequence. Mol Cell Biol 2000; 20(8):2890–901.PubMedCrossRefGoogle Scholar
  122. 122.
    Kim JK, Pedram A, Razandi M et al. Estrogen Prevents Cardiomyocyte Apoptosis through Inhibition of Reactive Oxygen Species and Differential Regulation of p38 Kinase Isoforms. J Biol Chem 2006; 281(10):6760–67.PubMedCrossRefGoogle Scholar
  123. 123.
    Patten RD, Pourati I, Aronovitz MJ et al. 17beta-estradiol reduces cardiomyocyte apoptosis in vivo and in vitro via activation of phospho-inositide-3 kinase/Akt signaling. Circ Res 2004; 95(7):692–99.PubMedCrossRefGoogle Scholar
  124. 124.
    Mattson MP, Robinson N, Guo Q. Estrogens stabilize mitochondrial function and protect neural cells against the pro-apoptotic action of mutant presenilin-1. Neuroreport 1997; 8(17):3817–21.PubMedCrossRefGoogle Scholar
  125. 125.
    Song RX, Santen RJ. Membrane initiated estrogen signaling in breast cancer. Biol Reprod 2006; 75(1):9–16.PubMedCrossRefGoogle Scholar
  126. 126.
    Kroemer G, Reed JC. Mitochondrial control of cell death. Nat Med 2000; 6(5):513–19.PubMedCrossRefGoogle Scholar
  127. 127.
    Ikeuchi M, Matsusaka H, Kang D et al. Overexpression of mitochondrial transcription factor a ameliorates mitochondrial deficiencies and cardiac failure after myocardial infarction. Circulation 2005; 112(5):683–90.PubMedCrossRefGoogle Scholar
  128. 128.
    Matsuyama S, Xu Q, Velours J et al. The Mitochondrial F0F1-ATPase proton pump is required for function of the proapoptotic protein Bax in yeast and mammalian cells. Mol Cell 1998; 1(3):327–36.PubMedCrossRefGoogle Scholar
  129. 129.
    Comelli M, Di Pancrazio F, Mavelli I. Apoptosis is induced by decline of mitochondrial ATP synthesis in erythroleukemia cells. Free Radic Biol Med 2003; 34(9):1190–99.PubMedCrossRefGoogle Scholar
  130. 130.
    Mills KI, Woodgate LJ, Gilkes AF et al. Inhibition of mitochondrial function in HL60 cells is associated with an increased apoptosis and expression of CD14. Biochem Biophys Res Commun 1999; 263(2):294–300.PubMedCrossRefGoogle Scholar
  131. 131.
    Wang J, Silva JP, Gustafsson CM et al. Increased in vivo apoptosis in cells lacking mitochondrial DNA gene expression. Proc Natl Acad Sci USA 2001; 98(7):4038–43.PubMedCrossRefGoogle Scholar
  132. 132.
    Wolvetang EJ, Johnson KL, Krauer K et al. Mitochondrial respiratory chain inhibitors induce apoptosis. FEBS Lett 1994; 339(1–2):40–44.PubMedCrossRefGoogle Scholar
  133. 133.
    Yager JD, Chen JQ. Mitochondrial estrogen receptors-new insights into specific functions. Trends Endocrinol Metab 2007; 18(3):89–91.PubMedCrossRefGoogle Scholar
  134. 134.
    yHsieh YC, Yu HP, Suzuki T et al. Upregulation of mitochondrial respiratory complex IV by estrogen receptor-beta is critical for inhibiting mitochondrial apoptotic signaling and restoring cardiac functions following trauma-hemorrhage. J Mol Cell Cardiol 2006; 41(3):511–21.CrossRefGoogle Scholar
  135. 135.
    Torroni A, Stepien G, Hodge JA et al. Neoplastic transformation is associated with coordinate induction of nuclear and cytoplasmic oxidative phosphorylation genes. J Biol Chem 1990; 265(33):20589–93.PubMedGoogle Scholar
  136. 136.
    Muss HB. Endocrine therapy for advanced breast cancer: a review. Breast Cancer Res Treat 1992; 21(1):15–26.PubMedCrossRefGoogle Scholar
  137. 137.
    Cardoso CM, Custodio JB, Almeida LM et al. Mechanisms of the deleterious effects of tamoxifen on mitochondrial respiration rate and phosphorylation efficiency. Toxicol Appl Pharmacol 2001; 176(3):145–52.PubMedCrossRefGoogle Scholar
  138. 138.
    Cardoso CM, Moreno AJ, Almeida LM et al. 4-Hydroxytamoxifen induces slight uncoupling of mitochondrial oxidative phosphorylation system in relation to the deleterious effects of tamoxifen. Toxicology 2002; 179(3):221–32.PubMedCrossRefGoogle Scholar
  139. 139.
    Cardoso CM, Moreno AJ, Almeida LM et al. Comparison of the changes in adenine nucleotides of rat liver mitochondria induced by tamoxifen and 4-hydroxytamoxifen. Toxicol In vitro 2003; 17(5–6):663–70.PubMedCrossRefGoogle Scholar
  140. 140.
    Tuquet C, Dupont J, Mesneau A et al. Effects of tamoxifen on the electron transport chain of isolated rat liver mitochondria. Cell Biol Toxicol 2000; 16(4):207–19.PubMedCrossRefGoogle Scholar
  141. 141.
    Kallio A, Zheng A, Dahllund J et al. Role of mitochondria in tamoxifen-induced rapid death of MCF-7 breast cancer cells. Apoptosis 2005; 10(6):1395–410.PubMedCrossRefGoogle Scholar
  142. 142.
    Zhao Y, Wang LM, Chaiswing L et al. Tamoxifen protects against acute tumor necrosis factor alpha-induced cardiac injury via improving mitochondrial functions. Free Radic Biol Med 2006; 40(7):1234–41.PubMedCrossRefGoogle Scholar
  143. 143.
    Besada V, Diaz M, Becker M et al. Proteomics of xenografted human breast cancer indicates novel targets related to tamoxifen resistance. Proteomics 2006; 6(3):1038–48.PubMedCrossRefGoogle Scholar
  144. 144.
    Strong R, Nakanishi T, Ross D et al. Alterations in the mitochondrial proteome of adriamycin resistant MCF-7 breast cancer cells. J Proteome Res 2006; 5(9):2389–95.PubMedCrossRefGoogle Scholar
  145. 145.
    Speirs V, Malone C, Walton DS et al. Increased expression of estrogen receptor beta mRNA in tamoxifen-resistant breast cancer patients. Cancer Res 1999; 59(21):5421–24.PubMedGoogle Scholar
  146. 146.
    Hopp TA, Weiss HL, Parra IS et al. Low levels of estrogen receptor beta protein predict resistance to tamoxifen therapy in breast cancer. Clin Cancer Res 2004; 10(22):7490–99.PubMedCrossRefGoogle Scholar
  147. 147.
    Lareef MH, Garber J, Russo PA et al. The estrogen antagonist ICI-182-780 does not inhibit the transformation phenotypes induced by 17-beta-estradiol and 4-OH estradiol in human breast epithelial cells. Int J Oncol 2005; 26(2):423–29.PubMedGoogle Scholar
  148. 148.
    Fan P, Wang J, Santen RJ et al. Long-term Treatment with Tamoxifen Facilitates Translocation of Estrogen Receptor {alpha} out of the Nucleus and Enhances its Interaction with EGFR in MCF-7 Breast Cancer Cells. Cancer Res 2007; 67(3):1352–60.PubMedCrossRefGoogle Scholar
  149. 149.
    Jasienska G, Thune I, Ellison PT. Energetic factors, ovarian steroids and the risk of breast cancer. Eur J Cancer Prev 2000; 9(4):231–39.PubMedCrossRefGoogle Scholar
  150. 150.
    Simopoulos AP. Energy imbalance and cancer of the breast, colon and prostate. Med Oncol Tumor Pharmacother 1990; 7(2–3):109–20.PubMedGoogle Scholar
  151. 151.
    Malin A, Matthews CE, Shu XO et al. Energy balance and breast cancer risk. Cancer Epidemiol Biomarkers Prev 2005; 14(6):1496–501.PubMedCrossRefGoogle Scholar
  152. 152.
    Silvera SA, Jain M, Howe GR et al. Energy balance and breast cancer risk: a prospective cohort study. Breast Cancer Res Treat 2005; 1–10.Google Scholar
  153. 153.
    Silvera SA, Jain M, Howe GR et al. Energy balance and breast cancer risk: a prospective cohort study. Breast Cancer Res Treat 2006; 97(1):97–106.PubMedCrossRefGoogle Scholar
  154. 154.
    Chang SC, Ziegler RG, Dunn B et al. Association of energy intake and energy balance with postmenopausal breast cancer in the prostate, lung, colorectal and ovarian cancer screening trial. Cancer Epidemiol Biomarkers Prev 2006; 15(2):334–41.PubMedCrossRefGoogle Scholar
  155. 155.
    Suzuki S, Platz EA, Kawachi I et al. Intakes of energy and macronutrients and the risk of benign prostatic hyperplasia. Am J Clin Nutr 2002; 75(4):689–97.PubMedGoogle Scholar
  156. 156.
    Warburg O. On the origin of cancer cells. Science 1956; 123(3191):309–14.PubMedCrossRefGoogle Scholar
  157. 157.
    Warburg O. On respiratory impairment in cancer cells. Science 1956; 124(3215):269–70.PubMedGoogle Scholar
  158. 158.
    Balinsky D, Platz CE, Lewis JW. Enzyme activities in normal, dysplastic and cancerous human breast tissues. J Natl Cancer Inst 1984; 72(2):217–24.PubMedGoogle Scholar
  159. 159.
    Garber K. Energy deregulation: licensing tumors to grow. Science 2006; 312(5777):1158–59.PubMedCrossRefGoogle Scholar
  160. 160.
    Isidoro A, Martinez M, Fernandez PL et al. Alteration of the bioenergetic phenotype of mitochondria is a hallmark of breast, gastric, lung and oesophageal cancer. Biochem J 2004; 378(Pt 1):17–20.PubMedCrossRefGoogle Scholar
  161. 161.
    Isidoro A, Casado E, Redondo A et al. Breast carcinomas fulfill the Warburg hypothesis and provide metabolic markers of cancer prognosis. Carcnogenesis 2005; 26(12):2095–104.CrossRefGoogle Scholar
  162. 162.
    Bi X, Lin Q, Foo TW et al. Proteomics analysis of colorectal cancer reveals alterations in metabolic pathways-mechanism of tumorigenesis. Mol Cell Proteomics 2006; 5(6):1119–30.PubMedCrossRefGoogle Scholar
  163. 163.
    Chen EI, Hewel J, Krueger JS et al. Adaptation of energy metabolism in breast cancer brain metastases. Cancer Res 2007; 67(4):1472–86.PubMedCrossRefGoogle Scholar
  164. 164.
    Pedersen PL, Mathupala S, Rempel A et al. Mitochondrial bound type II hexokinase: a key player in the growth and survival of many cancers and an ideal prospect for therapeutic intervention. Biochim Biophys Acta 2002; 1555(1–3):14–20.PubMedGoogle Scholar
  165. 165.
    Neeman M, Degani H. Metabolic studies of estrogen-and tamoxifen-treated human breast cancer cells by nuclear magnetic resonance spectroscopy. Cancer Res 1989; 49(3):589–94.PubMedGoogle Scholar
  166. 166.
    Rivenzon-Segal D, Boldin-Adamsky S, Seger D et al. Glycolysis and glucose transporter 1 as markers of response to hormonal therapy in breast cancer. Int J Cancer 2003; 107(2):177–82.PubMedCrossRefGoogle Scholar
  167. 167.
    Dakubo GD, Parr RL, Costello LC et al. Altered metabolism and mitochondrial genome in prostate cancer. J Clin Pathol 2006; 59(1):10–16.PubMedCrossRefGoogle Scholar
  168. 168.
    Juang HH. Modulation of iron on mitochondrial aconitase expression in human prostatic carcinoma cells. Mol Cell Biochem 2004; 265(1–2):185–94.PubMedCrossRefGoogle Scholar
  169. 169.
    Juang HH. Modulation of mitochondrial aconitase on the bionergy of human prostate carcinoma cells. Mol Genet Metab 2004; 81(3):244–52.PubMedCrossRefGoogle Scholar
  170. 170.
    Yadav RN. Isocitrate dehydrogenase activity and its regulation by estradiol in tissues of rats of various ages. Cell Biochem Funct 1988; 6(3):197–202.PubMedCrossRefGoogle Scholar
  171. 171.
    Copeland WC, Wachsman JT, Johnson FM et al. Mitochondrial DNA alterations in cancer. Cancer Invest 2002; 20(4):557–69.PubMedCrossRefGoogle Scholar
  172. 172.
    Chatterjee A, Mambo E, Sidransky D. Mitochondrial DNA mutations in human cancer. Oncogene 2006; 25(34):4663–74.PubMedCrossRefGoogle Scholar
  173. 173.
    Brandon M, Baldi P, Wallace DC. Mitochondrial mutations in cancer. Oncogene 2006; 25(34):4647–62.PubMedCrossRefGoogle Scholar
  174. 174.
    Krieg RC, Knuechel R, Schiffmann E et al. Mitochondrial proteome: cancer-altered metabolism associated with cytochrome c oxidase subun it level variation. Proteomics 2004; 4(9):2789–95.PubMedCrossRefGoogle Scholar
  175. 175.
    Capuano F, Varone D, D’Eri N et al. Oxidative phosphorylation and F(O)F(1) ATP synthase activity of human hepatocellular carcinoma. Biochem Mol Biol Int 1996; 38(5):1013–22.PubMedGoogle Scholar
  176. 176.
    Haugen DR, Fluge O, Reigstad LJ et al. Increased expression of genes encoding mitochondrial proteins in papillary thyroid carcinomas. Thyroid 2003; 13(7):613–20.PubMedCrossRefGoogle Scholar
  177. 177.
    Schulz TJ, Thierbach R, Voigt A et al. Induction of oxidative metabolism by mitochondrial frataxin inhibits cancer growth: Otto Warburg revisited. J Biol Chem 2006; 281(2):977–81.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2008

Authors and Affiliations

  • Jin-Qiang Chen
    • 1
  • Terry R. Brown
    • 2
  • James D. Yager
    • 3
  1. 1.Division of Pulmonary and Critical Care, Department of MedicineUniversity of Virginia School of MedicineCharlottesvilleUSA
  2. 2.Department of Biochemistry and Molecular BiologyJohns Hopkins Bloomberg School of Public HealthBaltimoreUSA
  3. 3.Department of Environmental Health SciencesJohns Hopkins Bloomberg Schoolof Public HealthBaltimoreUSA

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