Abstract
Progesterone (P) regulates several functions in cells through the interaction with its intracellular receptor (PR), which is a ligand-activated transcription factor that modifies the expression of genes involved in the control of cell growth and proliferation, such as vascular endothelial growth factor and epidermal growth factor receptor. Two PR isoforms have been reported: PR-B and PR-A, encoded by the same gene but with different function and regulation. It has been shown that PR isoforms are expressed in U373 and D54 cell lines, which are derived from grades III and IV of human astrocytomas, respectively. Our group has recently reported that P increases cell growth in both cells lines. The PR antagonist, RU486, blocked P effects and its treatment alone significantly reduced human astrocytomas cell growth in vitro. The over-expression of PR-A in U373 cells significantly reduced P effects. These data suggest that P regulates human astrocytomas cell growth through the interaction with PR and that PR-B/PR-A expression ratio is determinant in P functions in astrocytomas.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Altinoz MA, Bilir A, Ozar E, Onar FD, Sav A (2001) Medroxyprogesterone acetate alone or synergistic with chemotherapy suppresses colony formation and DNA synthesis in C6 glioma in vitro. Int J Dev Neurosci 19:541–547
Assimakopoulou M, Sotiropoulou-Bonikou G, Maraziotis T, Varakis J (1998) Does sex steroid receptor status have any prognostic or predictive significance in brain astrocytic tumors? Clin Neuropathol 17:27–34
Bonéy-Montoya J, Ziegler YS, Curtis CD, Montoya JA, Nardulli AM (2010) Long-range transcriptional control of progesterone receptor gene expression. Mol Endocrinol 24:346–358
Cabrera-Munoz E, Gonzalez-Arenas A, Saqui-Salces M, Camacho J, Larrea F, Garcia-Becerra R, Camacho-Arroyo I (2009) Regulation of progesterone receptor isoforms content in human astrocytoma cell lines. J Steroid Biochem Mol Biol 113:80–84
Camacho-Arroyo I (2003) Progesterone receptor isoforms expression and progesterone actions in the brain. In: Pandalai SG (ed) Recent Research Developments in Life Sciences. Research Signpost, Kerala, India, 221–242
Camacho-Arroyo I, Villamar-Cruz O, Gonzalez-Arenas A, Guerra-Araiza C (2002) Participation of the 26S proteasome in the regulation of progesterone receptor concentrations in the rat brain. Neuroendocrinology 76:267–271
Carroll RS, Zhang J, Dashner K, Sar M, Black PM (1995) Steroid hormone receptors in astrocytic neoplasms. Neurosurgery 37:496–503
Ellmann S, Sticht H, Thiel F, Beckmann MW, Strick R, Strissel PL (2009) Estrogen and progesterone receptors: from molecular structures to clinical targets. Cell Mol Life Sci 66:2405–2426
Gonzalez-Aguero G, Gutierrez AA, Gonzalez-Espinosa D, Solano JD, Morales R, Gonzalez-Arenas A, Cabrera-Munoz E, Camacho-Arroyo I (2007) Progesterone effects on cell growth of U373 and D54 human astrocytoma cell lines. Endocrine 32:129–135
Gonzalez-Aguero G, Ondarza R, Gamboa-Dominguez A, Cerbon MA, Camacho-Arroyo I (2001) Progesterone receptor isoforms expression pattern in human astrocytomas. Brain Res Bull 56:43–48
Guerra-Araiza C, Villamar-Cruz O, Gonzalez-Arenas A, Chavira R, Camacho-Arroyo I (2003) Changes in progesterone receptor isoforms content in the rat brain during the oestrous cycle and after oestradiol and progesterone treatments. J Neuroendocrinol 15:984–990
Hernandez-Hernandez T, Rodrıguez-Dorantes M, Gonzalez-Arenas A, Camacho-Arroyo I (2010) Progesterone and estradiol effects on SRC-1 and SRC-3 expression in human astrocytoma cell lines. Endocrine 37:194–200
Hulleman E, Helin K (2005) Molecular mechanisms in gliomagenesis. Adv Cancer Res 94:1–27
Ichimura K, Ohgaki H, Kleihues P, Collins VP (2004) Molecular pathogenesis of astrocytic tumours. J Neurooncol 70:137–160
Kastner P, Krust A, Turcotte B, Stropp U, Tora L, Gronemeyer H, Chambon P (1990) Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. EMBO J 9:1603–1614
Khalid H, Shibata S, Kishikawa M, Yasunaga A, Iseki M, Hiura T (1997) Immunohistochemical analysis of progesterone receptor and Ki-67 labeling index in astrocytic tumors. Cancer 80:2133–2140
Kraus WL, Montano MM, Katzenellenbogen BS (1994) Identification of multiple, widely spaced estrogen-responsive regions in the rat progesterone receptor gene. Mol Endocrinol 8:952–969
Lange CA, Shen T, Horwitz KB (2000) Phosphorylation of human progesterone receptors at serine-294 by mitogen-activated protein kinase signals their degradation by the 26S proteasome. Proc Natl Acad Sci USA 97:1032–1037
Leonhardt SA, Boonyaratanakornkit V, Edwards DP (2003) Progesterone receptor transcription and non-transcription signaling mechanisms. Steroids 68:761–770
Liu ZJ, Maekawa M, Horii T, Morita M (2003) The multiple promoter methylation profile of PR gene and ER alpha gene in tumor cell lines. Life Sci 73:1963–1972
McKenna NJ, Lanz RB, O’Malley BW (1999) Nuclear receptor coregulators: cellular and molecular biology. Endocr Rev 20:321–344
Momparler RL, Bovenzi V (2000) DNA methylation and cancer. J Cell Physiol 183:145–154
Mulac-Jericevic B, Mullinax RA, DeMayo FJ, Lydon JP, Conneely OM (2000) Subgroup of reproductive functions of progesterone mediated by progesterone receptor-B isoform. Science 289:1751–1754
Olson JJ, Beck DW, Schlechte J, Loh PM (1986) Hormonal manipulation of meningiomas in vitro. J Neurosurg 65:99–107
Pinski J, Halmos G, Shirahige Y, Wittliff JL, Schally AV (1993) Inhibition of growth of the human malignant glioma cell line (U87MG) by the steroid hormone antagonist RU486. J Clin Endocrinol Metab 77:1388–1392
Piroli G, Torres A, Grillo C, Lux-Lantos V, Aoki A, De Nicola AF (1998) Mechanisms in progestin antagonism of pituitary tumorigenesis. J Steroid Biochem Mol Biol 64:59–67
Richer JK, Jacobsen BM, Manning NG, Abel MG, Wolf DM, Horwitz KB (2002) Differential gene regulation by the two progesterone receptor isoforms in human breast cancer cells. J Biol Chem 277:5209–5218
Rosenfeld MG, Lunyak VV, Glass CK (2006) Sensors and signals: a coactivator/corepressor/epigenetic code for integrating signal-dependent programs of transcriptional response. Genes Dev 20:1405–1428
Rousseau A, Mokhtari K, Duyckaerts C (2008) The 2007 WHO classification of tumors of the central nervous system – what has changed? Curr Opin Neurol 21:720–727
Sager G, Orbo A, Jaeger R, Engstrom C (2003) Non-genomic effects of progestins–inhibition of cell growth and increased intracellular levels of cyclic nucleotides. J Steroid Biochem Mol Biol 84:1–8
Stening K, Eriksson O, Wahren L, Berg G, Hammar M, Blomqvist A (2007) Pain sensations to the cold pressor test in normally menstruating women: comparison with men and relation to menstrual phase and serum sex steroid levels. Am J Physiol Regul Integr Comp Physiol 293:R1711–R1716
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media B.V.
About this chapter
Cite this chapter
Camacho-Arroyo, I., Hansberg-Pastor, V., Cabrera-Muñoz, E., Hernández-Hernández, O.T., González-Arenas, A. (2012). Role of Progesterone Receptor Isoforms in Human Astrocytomas Growth. In: Hayat, M. (eds) Tumors of the Central Nervous System, Volume 5. Tumors of the Central Nervous System, vol 5. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2019-0_6
Download citation
DOI: https://doi.org/10.1007/978-94-007-2019-0_6
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-2018-3
Online ISBN: 978-94-007-2019-0
eBook Packages: MedicineMedicine (R0)