Thụ Thể Andrgenic và VEGF: Cơ Chế Điều Hòa Angiogenesis Bởi Andrgen Trong Ung Thư Tuyến Tiền Liệt

Cancers - Tập 9 Số 4 - Trang 32
Kurtis Eisermann1, Gail Fraizer2
1School of Biomedical Sciences, Kent State University, Kent, OH 44242, USA
2Department of Biological Sciences, Kent State University, Kent, OH, 44242 USA

Tóm tắt

Sự tiến triển của ung thư tuyến tiền liệt được kiểm soát bởi thụ thể androgen và sự hình thành mạch máu mới, hoặc angiogenesis, điều này thúc đẩy sự phát triển của ung thư tuyến tiền liệt di căn. Angiogenesis được kích thích bởi sự gia tăng biểu hiện của yếu tố tăng trưởng nội mô mạch máu (VEGF). VEGF bị điều hòa bởi nhiều yếu tố trong môi trường vi mô của khối u, bao gồm mức oxy thấp và nồng độ androgen cao. Ở đây, chúng tôi xem xét bằng chứng mô tả các cơ chế điều hòa VEGF qua hormone, bao gồm các tương tác mới giữa thụ thể androgen (AR), các yếu tố phiên mã epigenetic và zinc-finger, các biến thể AR và yếu tố thiếu oxy, HIF-1. Ý nghĩa của việc mô tả tác động của cả hormone và thiếu oxy lên biểu hiện VEGF và angiogenesis được tiết lộ trong các báo cáo gần đây về các liệu pháp lâm sàng nhắm mục tiêu vào cả con đường tín hiệu VEGF và AR. Việc hiểu rõ hơn về những phức tạp của biểu hiện VEGF có thể dẫn đến việc nhắm mục tiêu tốt hơn và kéo dài thời gian sống cho một nhóm bệnh nhân mắc ung thư tuyến tiền liệt kháng hormone di căn.

Từ khóa

#ung thư tuyến tiền liệt #thụ thể androgen #VEGF #angiogenesis #HIF-1 #yếu tố tăng trưởng nội mô mạch máu

Tài liệu tham khảo

Heinlein, 2004, Androgen receptor in prostate cancer, Endocr. Rev., 25, 276, 10.1210/er.2002-0032

Cleutjens, 1997, An androgen response element in a far upstream enhancer region is essential for high, androgen-regulated activity of the prostate-specific antigen promoter, Mol. Endocrinol., 11, 148, 10.1210/mend.11.2.9883

Tomlins, 2005, Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer, Science, 310, 644, 10.1126/science.1117679

Lin, 1999, Prostate-localized and androgen-regulated expression of the membrane-bound serine protease TMPRSS2, Cancer Res., 59, 4180

He, 1997, A novel human prostate-specific, androgen-regulated homeobox gene (NKX3. 1) that maps to 8p21, a region frequently deleted in prostate cancer, Genomics, 43, 69, 10.1006/geno.1997.4715

Magee, 2006, Direct, androgen receptor-mediated regulation of the FKBP5 gene via a distal enhancer element, Endocrinology, 147, 590, 10.1210/en.2005-1001

Kumar, 2009, Nuclear receptor coregulators in cancer biology, Cancer Res., 69, 8217, 10.1158/0008-5472.CAN-09-2223

Heemers, 2007, Androgen receptor (AR) coregulators: A diversity of functions converging on and regulating the AR transcriptional complex, Endocr. Rev., 28, 778, 10.1210/er.2007-0019

Agoulnik, I.U., and Weigel, N.L. (2008). Androgen Receptor Coactivators and Prostate Cancer. Hormonal Carcinogenesis V, Springer.

Wang, 2005, Androgen receptor corepressors: An overview, Prostate, 63, 117, 10.1002/pros.20170

Moyer, 2012, Screening for prostate cancer: US Preventive Services Task Force recommendation statement, Ann. Intern. Med., 157, 120, 10.7326/0003-4819-157-2-201207170-00459

Fox, 2002, Antibody to vascular endothelial growth factor slows growth of an androgen-independent xenograft model of prostate cancer, Clin. Cancer Res., 8, 3226

Delongchamps, 2006, Role of vascular endothelial growth factor in prostate cancer, Urology, 68, 244, 10.1016/j.urology.2006.03.010

Forsythe, 1996, Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1, Mol. Cell Biol., 16, 4604, 10.1128/MCB.16.9.4604

Stewart, 2001, Vascular endothelial growth factor expression and tumor angiogenesis are regulated by androgens in hormone responsive human prostate carcinoma: Evidence for androgen dependent destabilization of vascular endothelial growth factor transcripts, J. Urol., 165, 688, 10.1097/00005392-200102000-00095

Eisermann, 2013, Androgen up-regulates vascular endothelial growth factor expression in prostate cancer cells via an Sp1 binding site, Mol. Cancer, 12, 7, 10.1186/1476-4598-12-7

Joseph, 1997, Androgens regulate vascular endothelial growth factor content in normal and malignant prostatic tissue, Clin. Cancer Res., 3, 2507

Fraizer, G.C., Eisermann, K., Pandey, S., Brett-Morris, A., Bazarov, A., Nock, S., Ghimirey, N., and Kuerbitz, S.J. (2016). Functional Role of WT1 in Prostate Cancer. Wilms Tumor, Codon Publications.

McKay, 2016, A randomized phase II trial of short-course androgen deprivation therapy with or without bevacizumab for patients with recurrent prostate cancer after Definitive local therapy, J. Clin. Oncol., 34, 1913, 10.1200/JCO.2015.65.3154

Fernandez, 2015, Dual targeting of the androgen receptor and hypoxia-inducible factor 1alpha pathways synergistically inhibits castration-resistant prostate cancer cells, Mol. Pharmacol., 87, 1006, 10.1124/mol.114.097477

Loureiro, 2005, Transcriptional regulation of vascular endothelial growth factor in cancer, Cytokine Growth Factor Rev., 16, 77, 10.1016/j.cytogfr.2005.01.005

Ntekim, 2015, Regulation of vascular endothelial growth factor in prostate cancer, Endocr. Relat. Cancer, 22, R107, 10.1530/ERC-15-0123

Wagner, 2002, The Wilms' tumor gene Wt1 is required for normal development of the retina, EMBO J., 21, 1398, 10.1093/emboj/21.6.1398

Hanson, 2007, Regulation of vascular endothelial growth factor, VEGF, gene promoter by the tumor suppressor, WT1, Front Biosci., 12, 2279, 10.2741/2230

Sordello, 1998, Vascular endothelial growth factor is up-regulated in vitro and in vivo by androgens, Biochem. Biophys. Res. Commun., 251, 287, 10.1006/bbrc.1998.9328

Aslan, 2005, Vascular endothelial growth factor expression in untreated and androgen-deprived patients with prostate cancer, Pathol. Res. Pract., 201, 593, 10.1016/j.prp.2005.07.003

Smith, 2014, The regulation of spermatogenesis by androgens, Semin. Cell Dev. Biol., 30, 2, 10.1016/j.semcdb.2014.02.012

Metzger, 2005, LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription, Nature, 437, 436, 10.1038/nature04020

Kashyap, 2013, The lysine specific demethylase-1 (LSD1/KDM1A) regulates VEGF-A expression in prostate cancer, Mol. Oncol., 7, 555, 10.1016/j.molonc.2013.01.003

Cai, 2011, Androgen receptor gene expression in prostate cancer is directly suppressed by the androgen receptor through recruitment of lysine-specific demethylase 1, Cancer Cell, 20, 457, 10.1016/j.ccr.2011.09.001

Deng, 2016, Protein arginine methyltransferase 5 functions as an epigenetic activator of the androgen receptor to promote prostate cancer cell growth, Oncogene, 36, 1223, 10.1038/onc.2016.287

Levy, 1996, Post-transcriptional regulation of vascular endothelial growth factor by hypoxia, J. Biol. Chem., 271, 2746, 10.1074/jbc.271.5.2746

Levy, 1998, Hypoxic stabilization of vascular endothelial growth factor mRNA by the RNA-binding protein HuR, J. Biol. Chem., 273, 6417, 10.1074/jbc.273.11.6417

Shih, 1999, Regulation of human vascular endothelial growth factor mRNA stability in hypoxia by heterogeneous nuclear ribonucleoprotein L, J. Biol. Chem., 274, 1359, 10.1074/jbc.274.3.1359

Chang, 2013, Antagonistic function of the RNA-binding protein HuR and miR-200b in post-transcriptional regulation of vascular endothelial growth factor-A expression and angiogenesis, J. Biol. Chem., 288, 4908, 10.1074/jbc.M112.423871

Ray, 2009, A stress-responsive RNA switch regulates VEGFA expression, Nature, 457, 915, 10.1038/nature07598

Jafarifar, 2011, Repression of VEGFA by CA-rich element-binding microRNAs is modulated by hnRNP L, EMBO J., 30, 1324, 10.1038/emboj.2011.38

Arcondeguy, 2013, VEGF-A mRNA processing, stability and translation: A paradigm for intricate regulation of gene expression at the post-transcriptional level, Nucleic Acids Res., 41, 7997, 10.1093/nar/gkt539

Sun, 2014, Regulation of several androgen-induced genes through the repression of the miR-99a/let-7c/miR-125b-2 miRNA cluster in prostate cancer cells, Oncogene, 33, 1448, 10.1038/onc.2013.77

Morris, 2010, An RNA G-quadruplex is essential for cap-independent translation initiation in human VEGF IRES, J. Am. Chem. Soc., 132, 17831, 10.1021/ja106287x

Bornes, 2007, Translational induction of VEGF internal ribosome entry site elements during the early response to ischemic stress, Circ. Res., 100, 305, 10.1161/01.RES.0000258873.08041.c9

Sfar, 2006, Association of VEGF genetic polymorphisms with prostate carcinoma risk and clinical outcome, Cytokine, 35, 21, 10.1016/j.cyto.2006.07.003

Bornes, 2004, Control of the Vascular Endothelial Growth Factor Internal Ribosome Entry Site (IRES) Activity and Translation Initiation by Alternatively Spliced Coding Sequences, J. Biol. Chem., 279, 18717, 10.1074/jbc.M308410200

Levine, 1998, Androgens induce the expression of vascular endothelial growth factor in human fetal prostatic fibroblasts, Endocrinology, 139, 4672, 10.1210/endo.139.11.6303

Li, 2005, Upregulation of VEGF-C by androgen depletion: the involvement of IGF-IR-FOXO pathway, Oncogene, 24, 5510, 10.1038/sj.onc.1208693

Mabjeesh, 2003, Androgens stimulate hypoxia-inducible factor 1 activation via autocrine loop of tyrosine kinase receptor/phosphatidylinositol 3′-kinase/protein kinase B in prostate cancer cells, Clin. Cancer Res., 9, 2416

Wang, 2007, A hierarchical network of transcription factors governs androgen receptor-dependent prostate cancer growth, Mol. Cell, 27, 380, 10.1016/j.molcel.2007.05.041

Bolton, 2007, Cell- and gene-specific regulation of primary target genes by the androgen receptor, Genes Dev., 21, 2005, 10.1101/gad.1564207

Massie, 2007, New androgen receptor genomic targets show an interaction with the ETS1 transcription factor, EMBO Rep., 8, 871, 10.1038/sj.embor.7401046

Eisermann, K., Bazarov, A., Brett, A., Knapp, E., Piontkivska, H., and Fraizer, G. (2009, January 15–17). Uncovering androgen responsive regulatory networks in prostate cancer. Proceedings of the Ohio Collaborative Conference on Bioinformatics, Cleveland, OH, USA.

Mueller, 2000, Regulation of vascular endothelial growth factor (VEGF) gene transcription by estrogen receptors alpha and beta, Proc. Natl. Acad. Sci. USA, 97, 10972, 10.1073/pnas.200377097

Stoner, 2004, Estrogen regulation of vascular endothelial growth factor gene expression in ZR-75 breast cancer cells through interaction of estrogen receptor a and SP proteins, Oncogene, 23, 1052, 10.1038/sj.onc.1207201

Kimbro, 2006, Hypoxia-inducible factor-1 in human breast and prostate cancer, Endocr. Relat. Cancer, 13, 739, 10.1677/erc.1.00728

Zhong, 2004, Up-regulation of hypoxia-inducible factor 1α is an early event in prostate carcinogenesis, Cancer Detect. Prev., 28, 88, 10.1016/j.cdp.2003.12.009

Ragnum, 2013, Hypoxia-independent downregulation of hypoxia-inducible factor 1 targets by androgen deprivation therapy in prostate cancer, Int. J. Radiat. Oncol. Biol. Phys., 87, 753, 10.1016/j.ijrobp.2013.07.023

Horii, 2007, Androgen-dependent gene expression of prostate-specific antigen is enhanced synergistically by hypoxia in human prostate cancer cells, Mol. Cancer Res., 5, 383, 10.1158/1541-7786.MCR-06-0226

Mitani, 2012, Coordinated action of hypoxia-inducible factor-1alpha and beta-catenin in androgen receptor signaling, J. Biol. Chem., 287, 33594, 10.1074/jbc.M112.388298

Antonarakis, 2016, Androgen receptor variant-driven prostate cancer: Clinical implications and therapeutic targeting, Prostate Cancer Prostatic Dis., 19, 231, 10.1038/pcan.2016.17

Hörnberg, E., Ylitalo, E.B., Crnalic, S., Antti, H., Stattin, P., Widmark, A., Bergh, A., and Wikström, P. (2011). Expression of androgen receptor splice variants in prostate cancer bone metastases is associated with castration-resistance and short survival. PLoS ONE, 6.

Sun, 2010, Castration resistance in human prostate cancer is conferred by a frequently occurring androgen receptor splice variant, J. Clin. Investig., 120, 2715, 10.1172/JCI41824

Hu, 2009, Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate cancer, Cancer Res., 69, 16, 10.1158/0008-5472.CAN-08-2764

Efstathiou, 2015, Molecular characterization of enzalutamide-treated bone metastatic castration-resistant prostate cancer, Eur. Urol., 67, 53, 10.1016/j.eururo.2014.05.005

Antonarakis, 2014, AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer, N. Engl. J. Med., 371, 1028, 10.1056/NEJMoa1315815

Dehm, 2008, Splicing of a novel androgen receptor exon generates a constitutively active androgen receptor that mediates prostate cancer therapy resistance, Cancer Res., 68, 5469, 10.1158/0008-5472.CAN-08-0594

Wadosky, 2016, Molecular mechanisms underlying resistance to androgen deprivation therapy in prostate cancer, Oncotarget, 7, 64447, 10.18632/oncotarget.10901

Ferrer, 1997, Vascular endothelial growth factor (VEGF) expression in human prostate cancer: In situ and in vitro expression of VEGF by human prostate cancer cells, J. Urol., 157, 2329, 10.1016/S0022-5347(01)64775-X

Duque, 1999, Plasma levels of vascular endothelial growth factor are increased in patients with metastatic prostate cancer, Urology, 54, 523, 10.1016/S0090-4295(99)00167-3

Duque, 2006, Measurement of plasma levels of vascular endothelial growth factor in prostate cancer patients: Relationship with clinical stage, Gleason score, prostate volume, and serum prostate-specific antigen, Clinics, 61, 401, 10.1590/S1807-59322006000500006

Kelly, 2012, Randomized, double-blind, placebo-controlled phase III trial comparing docetaxel and prednisone with or without bevacizumab in men with metastatic castration-resistant prostate cancer: CALGB 90401, J. Clin. Oncol., 30, 1534, 10.1200/JCO.2011.39.4767