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Prostaglandins, Fatty Acids and Phospholipids in Normal and Neoplastic Breast Tissues

  • Grace Y. Sun
  • Benjamin S. Leung

Abstract

Regulation of mammary functions by hormonal factors is a complex phenomenon. Consequently, many of the biochemical mechanisms underlying various functional changes are not yet well understood. It is realized, however, that a disturbance of the regulatory mechanisms may result in abnormal functioning of the gland. Fatty acids and phospholipids are important not only as structural components of the mammary cell membranes, but also in regulating the membrane functions (72). Metabolism of the membrane lipids is generally governed by membrane-bound enzymes, some of which are hormonally regulated. The mammary gland lipids are altered during physiological changes such as from non-pregnant to pregnant states, pregnancy to lactation or neoplastic transformation of the gland. In this chapter, the compositional and metabolic changes of fatty acids and phospholipide of the mammary gland under different physiological conditions will be described and a comparison of the changes of neoplastic tissues with normal tissue will be made. Neoplastic cell transformation and tumor growth are also correlated to effects exerted by dietary lipids. A discussion of the mammary gland prostaglandine is included because these molecules are derived from polyunsaturated fatty acids, and they may play an important role in regulating the glandular functions, as well as tumorigenesis.

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References

  1. 1.
    Bennett A, Berstock DA, Raja B, Stamford IF. Survival time after surgery is inversely related to the amounts of prostaglandins extracted from human breast cancers. Br J Pharmacol 66: 451P, 1979.Google Scholar
  2. 2.
    Bennett A, Houghton J, Leaper DJ, Stamford IF. Cancer growth, response to treatment and survival time in mice: Beneficial effect of the prostaglandin synthesis inhibitor flurbiprofen. Prostaglandins 17: 179–191, 1979.CrossRefPubMedGoogle Scholar
  3. 3.
    Bhattacharya A, Vonderhaar BK. Phospholipid methylation stimulates lactogenic binding in mouse mammary gland membranes. Proc Natl Acad Sci USA 76: 4489–4492, 1979.CrossRefPubMedGoogle Scholar
  4. 4.
    Boyns AR, Buchan R, Cole EN, Forrest APM, Griffiths, K. Basal prolactin blood levels in three strains of rat with differing incidence of 7,12-dimethylbenz(a)anthracene induced mammary tumors. Eur J Cancer 9: 169–171, 1973.CrossRefPubMedGoogle Scholar
  5. 5.
    Brandorff NP. The effect of dietary fat on the fatty acid composition of lipids secreted in rats’ milk. Lipids 15: 276–278, 1980.CrossRefPubMedGoogle Scholar
  6. 6.
    Caffrey M, Infante JP, Kinsella JE. Isoenzymes of an acyltransferase from rabbit mammary gland: evidence from biphasic substrate saturation kinetics. FEBS Lett 52: 116–120, 1975.CrossRefPubMedGoogle Scholar
  7. 7.
    Caffrey M, Kinsella JE. Isoenzymes of an acyltransferase from rabbit mammary gland: solubilization of the micelle-specific species with Triton X-100. Biochem Biophys Res Commun 71: 484–491, 1976.CrossRefPubMedGoogle Scholar
  8. 8.
    Caffrey M, Kinsella JE. Properties of palmitoylCoA:Monopalmitoyl-sn-glycerol 3-phosphate palmitoyltransferase from rabbit mammary gland. Int J Biochem 9: 239–248, 1978.CrossRefPubMedGoogle Scholar
  9. 9.
    Carey EM, Dils R. The pattern of fatty acid synthesis in lactating rabbit mammary gland studied in vivo. Biochem J 126: 1005–1007, 1972.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Carroll KK, Hopkins GJ. Dietary polyunsaturated fat in relation to mammary carcinogenesis. Lipids 14: 155–158, 1979.CrossRefPubMedGoogle Scholar
  11. 11.
    Carroll KK, Khor HT. Effects of level and type of dietary fat on incidence of mammary tumors induced in female Sprague-Dawley rats by 7,12-dimethylbenz(a)anthracene. Lipids 6: 415–420, 1971.CrossRefPubMedGoogle Scholar
  12. 12.
    Chan PC, Head JF, Cohen LA, Wynder EL. Influence of dietary fat on the induction of mammary tumors by Nnitrosomethylurea: associated hormone changes and differences between Sprague-Dawley and F344 rats. J Natl Cancer Inst 59: 1279–1283, 1977.CrossRefPubMedGoogle Scholar
  13. 13.
    Cooper SM, Grigor MR. Stereospecific biosynthesis of triacylglycerols in mammary glands from lactating rats. Biochem J 174: 659–662, 1978.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Cooper SM, Grigor MR. Fatty acid specificities of microsomal acyltransferases esterifying positions-1 and -2 of acylglycerols in mammary glands from lactating rats. Biochem J 187: 289–295, 1980.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Dhami MSI, Feuer CF, Feuer G. Fatty acid changes in the hepatic endoplasmic reticulum during pregnancy in the rat. Res Commun Chem Pathol Pharmacol 23: 383–394, 1979.PubMedGoogle Scholar
  16. 16.
    Dies RP. Oxytocin test to demonstrate the initiation and end of lactation in rats. J Endocrin 40: 133–134, 1968.CrossRefGoogle Scholar
  17. 17.
    Dulbecco R, Bologna M, Unger M. Control of differentiation of a mammary cell line by lipids. Proc Natl Acad Sci USA 77: 1551–1555, 1980.CrossRefPubMedGoogle Scholar
  18. 18.
    Feldman EB, Carter AC. Circulating lipids and lipoproteins in women with metastatic breast carcinoma. J Clin Endocrinol Metab 33: 8–13, 1971.CrossRefPubMedGoogle Scholar
  19. 19.
    Gammal EB, Carroll KK, Plunkett ER. Effects of dietary fat on mammary carcinogenesis by 7,12-dimochylbenz(a)anthracene in rats. Cancer Res 27: 1737–1742, 1967.PubMedGoogle Scholar
  20. 20.
    Hallowes RC, Wang DY, Lewis DJ, Strong CR, Dils R. The stimulation by prolactin and growth hormone of fatty acid synthesis in explants from rat mammary glands. J Endocrinol 57: 265–276, 1973.CrossRefPubMedGoogle Scholar
  21. 21.
    Hansen JK, Knudsen J. Transacylation as a chain-termination mechanism in fatty acid synthesis by mammalian fatty acid synthetase. Synthesis of butyrate and hexanoate by lactating cow mammary gland fatty acid synthetase. Biochem J 15: 287–294, 1980.Google Scholar
  22. 22.
    Hilf R, Michel I, Bell C. Dose responses of R3230AC mammary tumor and mammary tissue to estrogen: Enzymes, nucleic acids, and lipids. Cancer Res 26: 865–870, 1966.PubMedGoogle Scholar
  23. 23.
    Hilf R, Michel I, Gibbs CC, Bell C. NADP-linked enzymes and lipids in normal and neoplastic tissue: Effects of estrogen and dietary glucose. Biochim Biophys Acta 116: 589–592, 1966.CrossRefPubMedGoogle Scholar
  24. 24.
    Hillyard LA, Abraham S. Effect of dietary polyunsaturated fatty acids on growth of mammary adenocarcinomas in mice and rats. Cancer Res 39: 4430–4437, 1979.PubMedGoogle Scholar
  25. 25.
    Hillyard LA, Rao GA, Abraham S. Effect of dietary fat on fatty acid composition of mouse and rat mammary adenocarcinomas (40781). Proc Soc Exp Biol Med 163: 376–383, 1980.CrossRefPubMedGoogle Scholar
  26. 26.
    Hopkins GJ, West CE. Effect of dietary polyunsaturated fat on the growth of a transplantable adenocarcinoma in C3HAfB mice. J Natl Cancer Inst 58: 753–756, 1977.CrossRefPubMedGoogle Scholar
  27. 27.
    Horrocks LA, Sun GY. Ethanolamine plasmalogens. pp 223231 in Research methods in Neurochemistry, Vol. 1, eds N Marks, R Rodnight. Plenum Publishing Co, New York, 1972Google Scholar
  28. 28.
    Hwang DW, Godke RA, Rings RW. Species variation in serum levels of prostaglandins and their precursor acids. Lipids 15: 597–600, 1980.CrossRefPubMedGoogle Scholar
  29. 29.
    Jensen EV, Desombre ER. Mechanism of action of the female sex hormones. Annu Rev Biochem 41: 203–230, 1972.CrossRefPubMedGoogle Scholar
  30. 30.
    Jubiz W, Frailey J, Smith JB. Inhibitory effect of prostaglandin F2 alpha on the growth of a hormone-dependent rat mammary tumor. Cancer Res 39: 998–1000, 1979.PubMedGoogle Scholar
  31. 31.
    Kano-Sueoka T, Cohen DM, Yamaizumi Z, Nishimura S, Mori M, Fujiki H. Phosphoethanolamine as a growth factor of a mammary carcinoma cell line of rat. Proc Natl Acad Sci USA 11: 5741–5744, 1979.CrossRefGoogle Scholar
  32. 32.
    Kidwell WR, Monaco ME, Wicha MS, Smith GS. Unsaturated fatty acid requirements for growth and survival of a rat mammary tumor cell line. Cancer Res 38: 4091–4100, 1978.PubMedGoogle Scholar
  33. 33.
    King MM, Bailey DM, Gibson DD, Pitha JV, McCay PB. Incidence and growth of mammary tumors induced by 7,12dimethylbenz[alanthracene as related to the dietary content of fat and antioxidant. J Natl Cancer Inst 63: 657–663, 1979.CrossRefPubMedGoogle Scholar
  34. 34.
    Kinsella JE. Glycerolipid synthesis in milk: Evidence of glycerol kinase and other biosynthetic enzymes. Int J Biochem 3: 89–92, 1972.CrossRefGoogle Scholar
  35. 35.
    Kinsella JE. Lipid composition and fatty acid metabolism by mammary cells of rat. Int J Biochem 4: 549–556, 1973.CrossRefGoogle Scholar
  36. 36.
    Kinsella JE. Preferential labeling of phosphatidylcholine during phospholipid synthesis by bovine mammary tissue. Lipids 8: 393–400, 1973.CrossRefPubMedGoogle Scholar
  37. 37.
    Kinsella JE. Biosynthesis of fatty acids in rat mammary cells. Int J Biochem 5: 417–421, 1974.CrossRefGoogle Scholar
  38. 38.
    Kinsella JE. Monoacyl-sn-glycerol 3-phosphate acyltransferase specificity in bovine mammary microsomes. Lipids 11: 680–684, 1976.CrossRefPubMedGoogle Scholar
  39. 39.
    Kinsella JE, Gross, M. Palmitic acid and initiation of mammary glyceride synthesis via phosphatidic acid. Biochim Biophys Acta 316: 109–113, 1973.CrossRefPubMedGoogle Scholar
  40. 40.
    Knazek RA, Liu SC, Bodwin JS, Vonderhaar BK. Requirement of essential fatty acids in the diet for development of the mouse mammary gland. J Natl Cancer Inst 64: 377–382, 1980.CrossRefPubMedGoogle Scholar
  41. 41.
    Knudsen J. Fatty acid synthetase from cow mammary gland tissue cells. Biochim Biophys Acta 280: 408–414, 1972.CrossRefPubMedGoogle Scholar
  42. 42.
    Kuhn J. Progesterone withdrawal as the lactogenic trigger in the rat. J Endocrinol 44: 39–54, 1969.CrossRefPubMedGoogle Scholar
  43. 43.
    Lands WEM, Crawford CG. Enzymes of membrane phospholipid metabolism in animals. pp 3–85 in The. Enzymgs of Biological Mgmbranes, Vol. 2, ed A Martonosi. Plenum Press, New York, 1976.Google Scholar
  44. 44.
    Leaper DJ, French BT, Bennett A. Breast Cancer and prostaglandins: A new approach to treatment. Br J Surg 66: 683–686, 1979.CrossRefPubMedGoogle Scholar
  45. 45.
    Leung BS. Hormonal dependency of experimental breast cancer. pp 219–261 in Hormones, Receptors, and Breast Cancer, ed WL McGuire. Raven Press, New York, 1978.Google Scholar
  46. 46.
    Leung BS, Sun GY. Acyl group composition of membrane phospholipids in mammary tissues and carcinoma induced by dimethylbenz(a)anthracene (39465). Proc Soc Exp Biol Med 152: 671–676, 1976.CrossRefPubMedGoogle Scholar
  47. 47.
    Libertini LJ, Smith S. Purification and properties of a thioesterase from lactating rat mammary gland which modifies the product specificity of fatty acid synthetase. J Biol Chem 253: 1393–1401, 1978.PubMedGoogle Scholar
  48. 48.
    Libertini LJ, Lin CY, Abraham S, Hilf R, Smith S. Medium chain fatty acid synthesis in rodent mammary adenocarcinomas in vitro. Biochim Biophys Acta 618: 185–191, 1980.CrossRefPubMedGoogle Scholar
  49. 49.
    Lin CY, Smith S. Properties of the thioesterase component obtained by limited trypsinization of the fatty acid synthetase multienzyme complex. J Biol Chem 253: 1954 1962, 1978.Google Scholar
  50. 50.
    Lin CY, Smith S, Abraham S. Fatty acid synthetase from a mouse mammary adenocarcinoma. Cancer Res 35: 3094–3099, 1975.PubMedGoogle Scholar
  51. 51.
    Marshall MO, Knudsen J. The specificity of 1-acyl-snglycerol 3-phosphate acyltransferase in microsomal fractions from lactating cow mammary gland towards short, medium and long chain acyl-CoA esters. Biochim Biophys Acta 489: 236–241, 1977.CrossRefPubMedGoogle Scholar
  52. 52.
    Marshall MO, Knudsen J. Specificity of diacylglycerol acyltransferase from bovine mammary gland, liver and adipose tissue towards acyl-CoA esters. Eur J Biochem 94: 93–98, 1979.CrossRefPubMedGoogle Scholar
  53. 53.
    Mayer RJ. Hormonal factors in lipogenesis in mammary gland. Vit Hormones 36: 101–163, 1978.CrossRefGoogle Scholar
  54. 54.
    McCarthy RD, Patton S. Biosynthesis of glycerides in freshly secreted milk. Nature (London) 202: 347–349, 1964.CrossRefGoogle Scholar
  55. 55.
    Rao GA, Abraham S. Fatty acid desaturation by mammary gland microsomes from lactating mice. Lipids 9: 269–271, 1974.CrossRefPubMedGoogle Scholar
  56. 56.
    Rao GA, Abraham S. Brief Communication: Enhanced growth rate of transplanted mammary adenocarcinoma induced in C3H mice by dietary linoleate. J Natl Cancer Inst 56: 431–432, 1976.CrossRefPubMedGoogle Scholar
  57. 57.
    Rillema JA. Activation of guanylate cyclase by activation in mammary gland homogenates from mice. Prostaglandins 15: 857–865, 1978.CrossRefPubMedGoogle Scholar
  58. 58.
    Rillema JA. Mechanism of prolactin action. Fed Proc 39: 2593–2598, 1980.PubMedGoogle Scholar
  59. 59.
    Rillema JA, Anderson LD. Phospholipases and the effect of prolactin on uridine incorporation into RNA in mammary gland explants of mice. Biochim Biophys Acta 428: 819824, 1976.CrossRefGoogle Scholar
  60. 60.
    Rillema JA, Mulder JA. Arachidonic acid distribution in lipids of mammary glands and DMBA-induced tumors of rats. Prostaglan Med 1: 31–38, 1978.CrossRefGoogle Scholar
  61. 61.
    Rillema JA, Wild EA. Prolactin activation of phospholipase A activity in membrane preparations from mammary glands. Endocrinology 100: 1219–1222, 1977.CrossRefPubMedGoogle Scholar
  62. 62.
    Rillema JA, Osmialowski EC, Linebaugh BE. Phospholipase A2 activity in 9,10-dimethyl-l,2-Benzanthracene-induced mammary tumors of rats. Biochim Biochem Acta 617: 150155, 1980.CrossRefGoogle Scholar
  63. 63.
    Rolland PH, Martin PM, Rolland AM, Toga M. Prostaglandins in human breast cancer. Identification of a cytosolic prostaglandin-9-keto-reductase activity. Biomedicine 31: 178–182, 1979.PubMedGoogle Scholar
  64. 64.
    Rolland PH, Martin PM, Jacquemier J, Rolland AM, Toga M. Prostaglandin in human breast cancer: Evidence suggesting that an elevated prostaglandin production is a marker of high metastatic potential for neoplastic cells. J Natl Cancer Inst 64: 1061–1070, 1980.PubMedGoogle Scholar
  65. 65.
    Shafie SM. Estrogen and the growth of breast cancer: New evidence suggests indirect action. Science 209: 701–702, 1980.CrossRefGoogle Scholar
  66. 66.
    Short VJ, Brindley DN, Dils R. Co-ordinate changes in enzymes of fatty acid synthesis, activation and esterification in rabbit mammary gland during pregnancy and lactation. Biochem J 162: 445–450, 1977.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Smith S, Abraham S. Fatty acid synthetase from lactating rat mammary gland. Studies on the termination sequence. J Biol Chem 246: 2537–2542, 1971.PubMedGoogle Scholar
  68. 68.
    Smith S, Abraham S. Fatty acid synthetase from lactating rat mammary gland. III. Dissociation and reassociation. J Biol Chem 246: 6428–6435, 1971.PubMedGoogle Scholar
  69. 69.
    Strong CR, Dils R. Fatty acids synthesized by mammary gland slices from lactating guinea pig and rabbit. Comp Biochem Physiol 43B: 643–652, 1972.CrossRefGoogle Scholar
  70. 70.
    Strong CR, Dils R. The fatty acid synthetase complex of lactating guinea-pig mammary gland. Int J Biochem 3: 369377, 1972.CrossRefGoogle Scholar
  71. 71.
    Strong CR, Forsyth I, Dils R. The effects of hormones on milk fat synthesis in mammary gland explants from pseudopregnant rabbits. Biochem J 128: 509–519, 1972.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Sun AY, Sun GY. Functional roles of phospholipids of synaptosomal membrane. pp 169–197 in function and Metabolism of Phospholipids in CNS and PNS, eds G Porcellati, L Amaducci, C Galli. Plenum Press, New York, 1976.Google Scholar
  73. 73.
    Sun GY, Leung BS. Changes in phospholipids and acyl group composition of rat mammary gland during pregnant, lactating, and post-weaning periods. Lipids 11: 322–327, 1976.CrossRefPubMedGoogle Scholar
  74. 74.
    Sun GY, Su KL, Der OM, Tang W. Enzymic regulation of arachidonate metabolism in brain membrane phosphoglycerides. Lipids 14: 229–235, 1979.CrossRefPubMedGoogle Scholar
  75. 75.
    Sun GY, Smith RE, Chan K, MacQuarrie R. Inhibition of acyl-CoA hydrolase activity in liver microsomes by lysophospholipids. Biochem Biophys Res Commun 94: 1278–1284, 1980.CrossRefPubMedGoogle Scholar
  76. 76.
    Tan WC, Chapman C, Takatori T, Privett OS. Studies of lipid class and fatty acid profiles of rat mammary tumors induced by 7,12-dimethylbenz(a)anthracene. Lipids 10: 7074, 1974.Google Scholar
  77. 77.
    Tan WC, Privett OS, Goldyne ME. Studies of prostaglandins in rat mammary tumors induced by 7,12-dimethylbenz(a)anthracene. Cancer Res 34: 3229–3231, 1974.PubMedGoogle Scholar
  78. 78.
    Tanioka H, Lin CY, Smith S, Abraham S. Acyl specificity in glyceride synthesis by lactating rat mammary gland. Lipids 9: 229–234, 1974.CrossRefPubMedGoogle Scholar
  79. 79.
    Wang DY, Hallowes RC, Bealing J, Strong CR, Dils R. The effect of prolactin and growth hormone on fatty acid synthesis by pregnant mouse mammary gland in organ culture. J Endocr 53: 311–321, 1972.CrossRefPubMedGoogle Scholar
  80. 80.
    Welsch CW, Brown CK, Goodrich-Smith M, Van J, Denenberg B, Anderson TM, Brooks CL. Inhibition of mammary tumori-genesis in carcinogen-treated Lewis rats by suppression of prolactin secretion. J Natl Cancer Inst 63: 1211–1214, 1979.PubMedGoogle Scholar
  81. 81.
    Weltzien HU. Cytolytic and membrane-perturbing properties of lysophosphatidylcholine. Biochim Biophys Acta 559: 259–287, 1979.CrossRefPubMedGoogle Scholar
  82. 82.
    Vermouth NT, Dies RP. Inhibitory effect of progesterone on the lactogenic and abortive action of prostaglandin F2a• J Endocrinol 66: 21–29, 1975.Google Scholar
  83. 83.
    Zalenski D, Hilf R. Effect of dietary carbohydrate on fatty acids in the R3230AC mammary adenocarcinoma (37193). Proc Soc Exp Biol Med 142: 1137–1140, 1973.CrossRefPubMedGoogle Scholar

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© Eden Press Inc. 1982

Authors and Affiliations

  • Grace Y. Sun
  • Benjamin S. Leung

There are no affiliations available

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