Molecular mechanisms affecting estrogen receptor levels in breast cancer

Yıl 2018, Cilt: 2 Sayı: 2, 137 - 142, 01.05.2018

Zehra Okat

https://doi.org/10.28982/josam.412314

Öz

The initiation of breast cancer, estrogen and its receptor (ER) perform significant functions. ER has two dissimilar forms, and they are commonly called as ER-alpha (-α) and ER-beta (-β). ERs are transcription factors. Expressions of ER-alpha (-α) protein are mainly arranged by the pathway of ubiquitin-proteasome. The hormone-responsive gene expression modulated by ER-α in addition to other nuclear receptors is a complicated process, which involves various cellular responses.  And also, ER-α levels are related with the pathology and etiology of breast cancer. In this review which is about the transcription and expression of the ER-α gene may provide the find out biochemical mechanisms behind the breast carcinogenesis. The regulation of ER expression, histone-modifying enzymes, Progesterone receptor (PR), peroxisome proliferator-activated receptors (PPAR), hydrocarbon receptor (AhR), Glucocorticoid receptor (GR), hypoxia and lysine residuals in ER region described in detail in this work. Increasing the number of these studies, are very significant for developing new methods of estrogen-dependent cancers. 

Anahtar Kelimeler

Breast cancer, Estrogen receptors, Progesterone receptor, Peroxisome proliferator-activated receptor, Aryl hydrocarbon receptor, Glucocorticoid receptor

Meme kanserinde östrojen reseptör seviyelerini etkileyen moleküler mekanizmalar

Öz

Meme kanserinin tetiklenmesinde, östrojen ve reseptörünün (ER) önemli işlevleri bulunmaktadır. ER'nin iki farklı şekli yer almakta ve bunlar ER-alfa (-α) ve ER-beta (-β) olarak adlandırılmaktadır. ER'ler birer transkripsiyon faktörüdür. ER-alfa (-α) proteininin ifadeleri esas olarak ubikuitin-proteazom yolağı ile düzenlenmektedir. Diğer nükleer reseptörlere ek olarak ER-alfa tarafından modüle edilen hormona duyarlı gen ekspresyonu, çeşitli hücresel tepkimeleri içeren karmaşık bir moleküler süreçtir. Ayrıca ER-α düzeyleri, meme kanseri patolojisi ve etyolojisi ile de ilişkilendirilmektedir. ER-α geninin transkripsiyonu ve ekspresyonu ile ilgili olan bu derleme yoluyla meme karsinojenezinin alt yapısında yer alan biyokimyasal mekanizmaların daha net anlaşılabileceği düşünülmektedir. ER ekspresyonu, histon değiştirici enzimler, Progesteron reseptörü (PR), peroksizom proliferatörü ile aktive edilmiş reseptörler (PPAR), aril-hidrokarbon reseptörü (AhR), Glukokortikoid reseptörü (GR), hipoksi ve ER bölgesinde yer alan lizinin kalıntılarının regülasyonu bu derlemede detaylı bir biçimde anlatılmaktadır. Buna benzer çalışmaların sayısının artırılması, östrojen bağımlı kanserler için yeni yöntemlerin geliştirilmesi açısından oldukça önemlidir.

Anahtar Kelimeler

Meme kanseri, Östrojen reseptörleri, Progesteron reseptörü, Peroksizom proliferatör aktive reseptör, Aril hidrokarbon reseptörü, Glukokortikoid reseptörü

Kaynakça

• 1. Roger P, Sahla ME, Makela S, Gustafsson JA, Baldet P, Rochefort H: Decreased expression of estrogen receptor beta protein in proliferative preinvasive mammary tumors. Cancer Res. 2001;61(6):2537-41. PMID: 11289127.
• 2. Hayashi SI, Eguchi H, Tanimoto K, Yoshida T, Omoto Y, Inoue A, Yoshida N, et al. The expression and function of estrogen receptor alpha and beta in human breast cancer and its clinical application. Endocr Relat Cancer. 2003;10(2):193-202. PMID: 12790782.
• 3. Berger SL. An embarrassment of niches: the many covalent modifications of histones in transcriptional regulation. Oncogene. 2001;20(24):3007-13. DOI: 10.1038/sj.onc.1204324
• 4. Lin HY, Chen CS, Lin SP, Weng JR, Chen CS. Targeting histone deacetylase in cancer therapy. Med Res Rev. 2006;26(4):397-413. DOI: 10.1002/med.20056.
• 5. Fukuda H, Sano N, Muto S, Horikoshi M. Simple histone acetylation plays a complex role in the regulation of gene expression. Brief Funct Genomic Proteomic. 2006;5(3):190-208. DOI: 10.1093/bfgp/ell032.
• 6. Tan J, Cang S, Ma Y, Petrillo RL, Liu D. Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents. Journal of Hematology & Oncology. 2010;3:5. doi: 10.1186/1756-8722-3-5.
• 7. Bieliauskas AV, Pflum MK. Isoform-selective histone deacetylase inhibitors. Chem Soc Rev. 2008;37(7):1402-13. doi: 10.1039/b703830p.
• 8. Watts CK, Sweeney KJ, Warlters A, Musgrove EA, Sutherland RL. Antiestrogen regulation of cell cycle progression and cyclin D1 gene expression in MCF-7 human breast cancer cells. Breast Cancer Res Treat. 1994;31(1):95–105. PMID: 7981461.
• 9. Herber B, Truss M, Beato M, Müller R. Inducible regulatory elements in the human cyclin D1 promoter. Oncogene. 1994;9(4):1295-304. PMID: 8134134.
• 10. Musgrove EA, Hamilton JA, Lee CS, Sweeney KJ, Watts CK, Sutherland RL. Growth factor, steroid, and steroid antagonist regulation of cyclin gene expression associated with changes in T-47D human breast cancer cell cycle progression. Mol Cell Biol. 1993;13(6):3577–87. PMID: 8497271 PMCID: PMC359827.
• 11. Wilcken NR, Prall OW, Musgrove EA, Sutherland RL. Inducible overexpression of cyclin D1 in breast cancer cells reverses the growth inhibitory effects of antiestrogens. Clin Cancer Res. 1997;3(6):849–54. PMID: 9815758.
• 12. Bartkova J, Lukas J, Müller H, Lützhoft D, Strauss M, Bartek J. Cyclin D1 protein expression and function in human breast cancer. Int J Cancer. 1994;57(3):353–61. PMID: 8168995.
• 13. Yoshida M, Horinouchi S, Beppu T. Trichostatin A and trapoxin: novel chemical probes for the role of histone acetylation in chromatin structure and function. Bioessays. 1995;17(5):423–30. DOI: 10.1002/bies.950170510.
• 14. Sherr CJ, Roberts JM. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 1999;13(12):1501–12.
• 15. Wang TC, Cardiff RD, Zukerberg L, Lees E, Arnold A, Schmidt EV. Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. Nature. 1994;369(6482):669–71. DOI: 10.1038/369669a0.
• 16. Lammie GA , Fantl V , Smith R , Schuuring E , Brookes S , Michalides R , Dickson C, et al. D11S287, a putative oncogene on chromosome 11q13, is amplified and expressed in squamous cell and mammary carcinomas and linked to BCL-1. Oncogene. 1991;6(3):439–44. PMID:2011398.
• 17. Ozasa H, Miyazawa S, Furuta S, Osumi T, Hashimoto T. Induction of peroxisomal β-oxidation enzymes in primary cultured rat hepatocytes by clofibric acid. Journal of Biochemistry. J Biochem. 1985;97(5):1273-8. PMID: 4030722.
• 18. Issemann I, Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature. 1990;347(6294):645-50. DOI: 10.1038/347645a0.
• 19. Goel SK, Lalwani ND, Reddy JK. Peroxisome proliferation and lipid peroxidation in rat liver. Cancer Research. 1986;46(3):1324-30.
• 20. Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schütz G, Umesono K, Blumberg B, et al. The nuclear receptor superfamily: the second decade. Cell. 1995;83(6):835-9.
• 21. Qin C, Burghardt R, Smith R, Wormke M, Stewart J, Safe S. Peroxisome Proliferator-activated Receptor Agonists Induce Proteasome-dependent Degradation of Cyclin D1 and Estrogen Receptor in MCF-7 Breast Cancer Cells. Cancer Res. 2003; 63(5):958-64. PMID: 12615709.
• 22. Gupta R1, Brockman JA, Sarraf P, Willson TM, DuBois RN. Target genes of peroxisome proliferator-activated receptor in colorectal cancer cells. J Biol Chem. 2001;276(32):29681-7. DOI: 10.1074/jbc.M103779200.
• 23. Swanson HI, Bradfield CA. The AH-receptor: genetics, structure and function. Pharmacogenetics. 1993;3(5):213-30.
• 24. Barouki R, Coumoul X, Fernandez-Salguero PM. The Aryl Hydrocarbon Receptor, More than a Xenobiotic-Interacting Protein. FEBS Letters. 2007;Vol. 581(No. 19):3608–15. [PubMed: 17412325]
• 25. Sherr DH. Another Important Biological Function for the Aryl Hydrocarbon Receptor. Arteriosclerosis Thrombosis and Vascular Biology. 2011;31(6):1247–48. DOI: https://doi.org/10.1161/ATVBAHA.111.227553.
• 26. Wormke M, Stoner M, Savill B, Walker K, Abdelrahim M, Burghardt R, Safe S. The Aryl Hydrocarbon Receptor Mediates Degradation of Estrogen Receptor through Activation of Proteasomes molecular and cellular biology. 2003;23(6):1843–55. doi: 10.1128/MCB.23.6.1843-1855.2003.
• 27. Safe S, Qin C, McDougal A. Development of selective aryl hydrocarbon receptor modulators for treatment of breast cancer. Expert Opin Invest Drugs. 1999;8:1385-96.
• 28. McDougal A, Wormke M, Calvin J, Safe S. Tamoxifen-induced antitumorigenic/antiestrogenic action synergized by a selective Ah receptor modulator. Cancer Res. 2001;61:3901–07. PMID: 11358803.
• 29. Romkes M, Safe S. Comparative activities of 2,3,7,8-tetrachlorodibenzo-p-dioxin and progesterone as antiestrogens in the female rat uterus. Toxicol Appl Pharmacol. 1988;92:368-80.
• 30. Nawaz Z, Lonard DM, Dennis AP, Smith CL and O'Malley BW. Proteasome-dependent degradation of the human estrogen receptor. Proc Natl Acad Sci. 1999;96:1858-62.
• 31. McKenna NJ, O'Malley BW. Combinatorial control of gene expression by nuclear receptors and coregulators. Cell. 2002;108:465–74.
• 32. Bamberger CM, Schulte HM, Chrousos GP. Molecular determinants of glucocorticoid receptor function and tissue sensitivity to glucocorticoids. Endocr Rev. 1996;17:245–61. DOI: 10.1210/edrv-17-3-245.
• 33. Gibson S, Tu S, Oyer R, Anderson SM, Johnson GL. Epidermal growth factor protects epithelial cells against Fas-induced apoptosis. Requirement for Akt activation. J Biol Chem. 1999;274:17612–8. PMID: 10364198.
• 34. Kinyamu HK, Archer TK. Estrogen Receptor-Dependent Proteasomal Degradation of the Glucocorticoid Receptor Is Coupled to an Increase in Mdm2 Protein Expression Mol Cell Biol. 2003;23(16):5867-81. PMCID: PMC166332.
• 35. Bunn HF, Poyton RO. 1996 Oxygen sensing and molecular adaptation to hypoxia. Physiol Rev. 1996;76:839–85.
• 36. Aplin JD. 2000 Hypoxia and human placental development. J Clin Invest. 2000;105(5):559–60. doi: 10.1172/JCI9512.
• 37. Semenza GL. 2000 HIF-1 and human disease: one highly involved factor. Genes Dev. 2000;15;14(16):1983-91. PMID: 10950862.
• 38. Bos R, Zhong H, Hanrahan CF, Mommers EC, Semenza GL, Pinedo HM, Abeloff MD, et al. Levels of hypoxia-inducible factor-1 during breast carcinogenesis. J Natl Cancer Inst. 2001;93(4):309-14. PMID: 11181778
• 39. Fisher B, Costantino J, Redmond C, Poisson R, Bowman D, Couture J, Dimitrov NV, et al. 1989 A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. N Engl J Med. 1989;320(8):479-84. DOI: 10.1056/NEJM198902233200802.
• 40. Stoner M, Safe S. Vascular endothelial growth factor (VEGF) is induced by 17 -estradiol in ZR-75 human breast cancer cell line. Toxicologist 2001;153 (Abstract).
• 41. Stoner M, Saville B, Wormke M, Dean D, Burghardt R, Safe S. Hypoxia induces proteasome-dependent degradation of estrogen receptor alpha in ZR-75 breast cancer cells. Mol Endocrinol. 2002;16(10):2231-42. DOI: 10.1210/me.2001-0347.
• 42. Wei LL, Krett NL, Francis MD, Gordon DF, Wood WM, O’Malley BW & Horwitz KB. Mol. Endocrinol. 1988;2:62–72.
• 43. Horwitz KB & McGuire WL. Specific progesterone receptors in human breast cancer. Steroids. 1975;25:497–505.
• 44. Lange CA, Shen T, Horwitz KB. Phosphorylation of human progesterone receptors at serine-294 by mitogen-activated protein kinase signals their degradation by the 26S proteasome. Proc Natl Acad Sci U S A. 2000;97(3):1032-7. PMCID: PMC15511.
• 45. Nardulli AM & Katzenellenbogen BS. Endocrinology 1988; 122, 1532– 40.
• 46. Berry NB, Fan M, Nephew KP. Estrogen Receptor-α Hinge-Region Lysines 302 and 303 Regulate Receptor Degradation by the Proteasome Mol Endocrinol. 2008;22(7):1535-51. doi: 10.1210/me.2007-0449.
• 47. Whitesell L, Lindquist SL. HSP90 and the chaperoning of cancer. Nat Rev Cancer. 2005;5:761–72. DOI: 10.1038/nrc1716.
• 48. Tateishi Y, Kawabe Y, Chiba T, Murata S, Ichikawa K, Murayama A, Tanaka K, et al. Ligand-dependent switching of ubiquitin-proteasome pathways for estrogen receptor. EMBO J. 2004;23:4813–23. DOI: 10.1038/sj.emboj.7600472.
• 49. Pratt WB. The role of the hsp90-based chaperone system in signal transduction by nuclear receptors and receptors signaling via MAP kinase. Annu Rev Pharmacol Toxicol. 1997;37:297–326. DOI: 10.1146/annurev.pharmtox.37.1.297.
• 50. Luders J, Demand J, Hohfeld J. The ubiquitin-related BAG-1 provides a link between the molecular chaperones Hsc70/Hsp70 and the proteasome. J Biol Chem. 2000;275:4613–7. PMID: 10671488.
• 51. Freeman BC, Felts SJ, Toft DO, Yamamoto KR. The p23 molecular chaperones act at a late step in intracellular receptor action to differentially affect ligand efficacies. Genes Dev. 2000;14:422–434. PMCID: PMC316379.
• 52. Connell P, Ballinger CA, Jiang J, Wu Y, Thompson LJ, Hohfeld J, Patterson C. The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nat Cell Biol. 2001;3:93–6. DOI: 10.1038/35050618.