PGRMC1蛋白功能及其在肿瘤发生发展中的作用
The Function of PRGMC1 and Its Role in Tumorgenesis and Tumor Development
DOI: 10.12677/HJBM.2013.32002, PDF, HTML, XML, 下载: 4,320  浏览: 16,025  国家自然科学基金支持
作者: 马 雯*, 夏祥颖, 梁淑芳:四川大学华西医院生物治疗国家重点实验室,成都
关键词: PGRMC1蛋白肿瘤标志物PGRMC1; Cancer; Biomarker
摘要: 孕酮受体膜组分1蛋白(PGRMC1)在乳腺癌,甲状腺癌,结肠癌,卵巢癌和肺癌等多种肿瘤组织和肿瘤细胞系中高表达。PGRMC1蛋白在肿瘤的生长和促进肿瘤细胞的存活中发挥作用,它还可以抵制肿瘤细胞凋亡,促进锚着独立生长,侵袭以及肿瘤生长和转移。PGRMC1蛋白还调节胆固醇合成,其信号转导对于癌症的发展是非常重要的,进一步深入研究PGRMC1蛋白与肿瘤发生的关系有助于寻找新的肿瘤标志物,将为肿瘤的早期诊断与预后以及有效药物靶点的发现提供理论和实验依据。
Abstract: Progesterone receptor membrane component 1 (PGRMC1) is overexpressed in breast, colon, ovarian, lung and thyroid tumor tissues, as well as in cancer cell lines. PGRMC1 is associated with tumor growth and development, and it also can resist apoptosis of tumor cells, promote tumor growth independently and benefit to invasion and metas-tasis of tumor. PGRMC1 regulates cholesterol synthesis and signal transduction. Further studies on the relationship be-tween PGRMC1 and tumorigenesis will help to find new cancer biomarkers, which will provide theoretical and experi-mental evidences for early diagnosis and prognosis, as well as effective drug target for cancer.
文章引用:马雯, 夏祥颖, 梁淑芳. PGRMC1蛋白功能及其在肿瘤发生发展中的作用[J]. 生物医学, 2013, 3(2): 7-11. http://dx.doi.org/10.12677/HJBM.2013.32002

参考文献

[1] M. A. Cahill. Progesterone receptor membrane component 1: An integrative review. The Journal of Steroid Biochemistry and Mo- lecular Biology, 2007, 105: 16-36.
[2] R. M. Lösel, D. Besong, J. J. Peluso and M. Wehling. Proges- terone receptor membrane component 1—Many tasks for a ver- satile protein. Steroids, 2008, 73(9-10): 929-934.
[3] R. A. Hand, R. J. Craven. Hpr6.6 protein mediates cell death from oxidative damage in MCF-7 human breast cancer cells. Journal of Cellular Biochemistry, 2003, 90(3): 534-547.
[4] J. J. Peluso, A. Pappalardo, R. Losel and M. Wehling. Proges- terone membrane receptor component 1 expression in the im- mature rat ovary and its role in mediating progesterone’s an- tiapoptotic action. Endocrinology, 2006, 147(6): 3133-3140.
[5] S. Difilippantonio, Y. Chen, A. Pietas, et al. Gene expression profiles in human non-small and small-cell lung cancers. European Journal of Cancer, 2003, 39(13): 1936-1947.
[6] H. Neubauer, S. E. Clare, W. Wozny, et al. Breast cancer pro- teomics reveals correlation between estrogen receptor status and differential phosphorylation of PGRMC1. Breast Cancer Re- search, 2008, 10(5): R85.
[7] J. J. Peluso, X. Liu, M. M. Saunders, et al. Regulation of ovarian cancer cell viability and sensitivity to cisplatin by progesterone receptor membrane component-1. Journal of Clinical Endocri- nology & Metabolism, 2008, 93(5): 1592-1599.
[8] G. Crudden, R. Loesel and R. J. Craven. Overexpression of the cytochrome p450 activator hpr6 (heme-1 domain protein/human progesterone receptor) in tumors. Tumour Biology, 2005, 26(3): 142-146.
[9] R. J. Craven. PGRMC1: A new biomarker for the estrogen re- ceptor in breast cancer. Breast Cancer Research, 2008, 10(5): 113.
[10] S. A. Beausoleil, M. Jedrychowski, D. Schwartz, et al. Large- scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences USA, 2004, 101(33): 12130-12135.
[11] J. C. Mallory, G. Crudden, A. Oliva, et al. A novel group of genes regulates susceptibility to antineoplastic drugs in highly tumorigenic breast cancer cells. Molecular Pharmacology, 2005, 68(6): 1747-1756.
[12] G. Crudden, R. E. Chitti and R. J. Craven. Hpr6 (heme-1 domain protein) regulates the susceptibility of cancer cells to chemo- therapeutic drugs. Journal of Pharmacology and Experimental Therapeutics, 2006, 316(1): 448-455.
[13] C. J. Krebs, E. D. Jarvis, J. Chan, et al. A membrane-associated progesterone-binding protein, 25-Dx, is regulated by progester- one in brain regions involved in female reproductive behaviors. Proceedings of the National Academy of Sciences USA, 2000, 97(23): 12816-12821.
[14] A. L. Hughes, D. W. Powell and M. Bard. Dap1/PGRMC1 binds and regulates cytochrome P450 enzymes. Cell Metabolism, 2007, 5(2): 143-149.
[15] J. J. Peluso, A. Pappalardo and G. Fernandez. Involvement of an unnamed protein, RDA288, in the mechanism through which progesterone mediates its antiapoptotic action in spontaneously immortalized granulosa cells. Endocrinology, 2004, 145(6): 3014- 3022.
[16] G. I. Lepesheva, M. R. Waterman. Sterol 14alpha-demethylase cytochrome P450(CYP51), a P450 in all biological kingdoms. Biochimica et Biophysica Acta, 2007, 1770(3): 467-477.
[17] R. J. Craven, J. C. Mallory and R. A. Hand. Regulation of iron homeostasis mediated by the heme-binding protein Dap1 (dam- age resistance protein 1) via the P450 protein Erg11/Cyp51. The Journal of Biological Chemistry, 2007, 282(50): 36543-36551.
[18] J. C. Mallory, G. Crudden and B. L. Johnson. Dap1p, a heme- binding protein that regulates the cytochrome P450 protein Erg11p/Cyp51p in Saccharomyces cerevisiae. Molecular and Cellular Biology, 2005, 25(5): 1669-1679.
[19] M. Suchanek, A. Radzikowska and C. Thiele. Photo-leucine and photo-methionine allow identification of protein-protein interac- tions in living cells. Nature Methods, 2005, 2(4): 261-267.
[20] J. L. Goldstein, R. A. DeBose-Boyd and M. S. Brown. Protein sensors for membrane sterols. Cell, 2006, 124(1): 35-46.
[21] J. J. Peluso, J. Romak and X. Liu. Progesterone receptor mem- brane component-1 (PGRMC1) is the mediator of progesterone’s antiapoptotic action in spontaneously immortalized granulosa cells as revealed by PGRMC1 small interfering ribonucleic acid treatment and functional analysis of PGRMC1 mutations. Endo- crinology, 2008, 149(2): 534-543.
[22] A. Gompel, S. Somai, M. Chaouat, et al. Hormonal regulation of apoptosis in breast cells and tissues. Steroids, 2000, 65(10-11): 593-598.
[23] L. Engmann, R. Losel, M. Wehling and J. J. Peluso. Progester- one regulation of human granulosa/luteal cell viability by an RU486-independent mechanism. Journal of Clinical Endocri- nology & Metabolism, 2006, 91(12): 4962-4968.
[24] J. J. Peluso, G. Fernandez, A. Pappalardo and B. A. White. Char- acterization of a putative membrane receptor for progesterone in rat granulosa cells. Biology of Reproduction, 2001, 65: 94-101.
[25] H. J. Rohe, I. S. Ahmed, K. E. Twist and R. J. Craven. PGRMC1 (progesterone receptor membrane component 1): A targetable protein with multiple functions in steroid signaling, P450 activa- tion and drug binding. Pharmacology & Therapeutics, 2009, 121(1): 14-19.