Androgen receptor splice variants activating the full-length receptor in mediating resistance to androgen-directed therapy

Oncotarget

Volumn 5, Issue 6, 2014, Pages 1646-1656

  Cao, Bo ^a,b   Qi, Yanfeng ^a   Zhang, Guanyi ^a,b   Xu, Duo ^a,b   Zhan, Yang ^a   Alvarez, Xavier ^c   Guo, Zhiyong ^d   Fu, Xueqi ^b   Plymate, Stephen R ^e   Sartor, Oliver ^a   Zhang, Haitao ^a,b   Dong, Yan ^a,b  

^a TULANE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b JILIN UNIVERSITY   (China)

^c TULANE NATIONAL PRIMATE RESEARCH CENTER   (United States)

^d UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

Androgen receptor; Castration resistance; Enzalutamide; Prostate cancer; Splice variant

Indexed keywords

ANDROGEN RECEPTOR; ANDROGEN RECEPTOR SPLICE VARIANT; ENZALUTAMIDE; UNCLASSIFIED DRUG; ANDROGEN; AR PROTEIN, HUMAN; ISOPROTEIN; MESSENGER RNA; PHENYLTHIOHYDANTOIN;

ANDROGEN THERAPY; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CELL GROWTH; CONTROLLED STUDY; GENE CONTROL; GENE EXPRESSION; GENE TARGETING; IN VIVO STUDY; MOUSE; NONHUMAN; NUCLEAR LOCALIZATION SIGNAL; PROMOTER REGION; PROSTATE CANCER; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN TARGETING; RECEPTOR OCCUPANCY; TUMOR RESISTANCE; TUMOR XENOGRAFT; ANALOGS AND DERIVATIVES; ANIMAL; APOPTOSIS; CELL FRACTIONATION; CELL NUCLEUS; CELL PROLIFERATION; CHROMATIN IMMUNOPRECIPITATION; DRUG EFFECTS; DRUG RESISTANCE; DRUG SCREENING; GENE EXPRESSION REGULATION; GENETICS; HUMAN; MALE; METABOLISM; NEOPLASMS, HORMONE-DEPENDENT; NUDE MOUSE; PATHOLOGY; PROSTATIC NEOPLASMS, CASTRATION-RESISTANT; PROTEIN TRANSPORT; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA SPLICING; TRANSCRIPTION INITIATION; TUMOR CELL CULTURE;

ANDROGENS; ANIMALS; APOPTOSIS; CELL NUCLEUS; CELL PROLIFERATION; CHROMATIN IMMUNOPRECIPITATION; DRUG RESISTANCE, NEOPLASM; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MALE; MICE; MICE, NUDE; NEOPLASMS, HORMONE-DEPENDENT; PHENYLTHIOHYDANTOIN; PROMOTER REGIONS, GENETIC; PROSTATIC NEOPLASMS, CASTRATION-RESISTANT; PROTEIN ISOFORMS; PROTEIN TRANSPORT; REAL-TIME POLYMERASE CHAIN REACTION; RECEPTORS, ANDROGEN; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA SPLICING; RNA, MESSENGER; SUBCELLULAR FRACTIONS; TRANSCRIPTIONAL ACTIVATION; TUMOR CELLS, CULTURED; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84904256379     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.1802     Document Type: Article

References (39)

1. Egan A, Dong Y, Zhang H, Qi Y, Balk SP, Sartor O. Castration-resistant prostate cancer: Adaptive responses in the androgen axis. Cancer Treat.Rev. 2014; 40: 426-33.
2. Knudsen KE, Scher HI. Starving the addiction: new opportunities for durable suppression of AR signaling in prostate cancer. Clin.Cancer Res. 2009; 15: 4792-8.
3. Chen CD, Welsbie DS, Tran C, Baek SH, Chen R, Vessella R, Rosenfeld MG, Sawyers CL. Molecular determinants of resistance to antiandrogen therapy. Nat.Med. 2004; 10: 33- 9.
4. Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ, Staffurth JN, North S, Vogelzang NJ, Saad F, Mainwaring P, Harland S, Goodman OB, Jr., Sternberg CN, Li JH, Kheoh T et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, doubleblind, placebo-controlled phase 3 study. Lancet Oncol. 2012; 13: 983-92.
5. Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, de WR, Mulders P, Chi KN, Shore ND, Armstrong AJ, Flaig TW, Flechon A, Mainwaring P, Fleming M, Hainsworth JD et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N.Engl.J.Med. 2012; 367: 1187-97.
6. Hornberg E, Ylitalo EB, Crnalic S, Antti H, Stattin P, Widmark A, Bergh A, Wikstrom P. Expression of androgen receptor splice variants in prostate cancer bone metastases is associated with castration-resistance and short survival. PLoS One. 2011; 6: e19059.
7. Hu R, Lu C, Mostaghel EA, Yegnasubramanian S, Gurel M, Tannahill C, Edwards J, Isaacs WB, Nelson PS, Bluemn E, Plymate SR, Luo J. Distinct transcriptional programs mediated by the ligand-dependent full-length androgen receptor and its splice variants in castration-resistant prostate cancer. Cancer Res. 2012; 72: 3457-62.
8. Li Y, Chan SC, Brand LJ, Hwang TH, Silverstein KA, Dehm SM. Androgen receptor splice variants mediate enzalutamide resistance in castration-resistant prostate cancer cell lines. Cancer Res. 2012; 73: 483-9.
9. Liu LL, Xie N, Sun S, Plymate S, Mostaghel E, Dong X. Mechanisms of the androgen receptor splicing in prostate cancer cells. Oncogene. 2013 Jul 15; [Epub ahead of print].
10. Mostaghel EA, Marck BT, Plymate SR, Vessella RL, Balk S, Matsumoto AM, Nelson PS, Montgomery RB. Resistance to CYP17A1 Inhibition with Abiraterone in Castration- Resistant Prostate Cancer: Induction of Steroidogenesis and Androgen Receptor Splice Variants. Clinical Cancer Research. 2011; 17: 5913-25.
11. Nadiminty N, Tummala R, Liu C, Yang J, Lou W, Evans CP, Gao AC. NF-kappaB2/p52 Induces Resistance to Enzalutamide in Prostate Cancer: Role of Androgen Receptor and Its Variants. Mol.Cancer Ther. 2013; 12: 1629-37.
12. Dehm SM, Schmidt LJ, Heemers HV, Vessella RL, Tindall DJ. Splicing of a novel androgen receptor exon generates a constitutively active androgen receptor that mediates prostate cancer therapy resistance. Cancer Res. 2008; 68: 5469-77.
13. Guo Z, Yang X, Sun F, Jiang R, Linn DE, Chen H, Chen H, Kong X, Melamed J, Tepper CG, Kung HJ, Brodie AM, Edwards J, Qiu Y. A novel androgen receptor splice variant is up-regulated during prostate cancer progression and promotes androgen depletion-resistant growth. Cancer Res. 2009; 69: 2305-13.
14. Hu R, Dunn TA, Wei S, Isharwal S, Veltri RW, Humphreys E, Han M, Partin AW, Vessella RL, Isaacs WB, Bova GS, Luo J. Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormonerefractory prostate cancer. Cancer Res. 2009; 69: 16-22.
15. Sun S, Sprenger CC, Vessella RL, Haugk K, Soriano K, Mostaghel EA, Page ST, Coleman IM, Nguyen HM, Sun H, Nelson PS, Plymate SR. Castration resistance in human prostate cancer is conferred by a frequently occurring androgen receptor splice variant. J.Clin.Invest. 2010; 120: 2715-30.
16. Zhang X, Morrissey C, Sun S, Ketchandji M, Nelson PS, True LD, Vakar-Lopez F, Vessella RL, Plymate SR. Androgen receptor variants occur frequently in castration resistant prostate cancer metastases. PLoS One. 2011; 6: e27970.
17. Yamashita S, Lai KP, Chuang KL, Xu D, Miyamoto H, Tochigi T, Pang ST, Li L, Arai Y, Kung HJ, Yeh S, Chang C. ASC-J9 suppresses castration-resistant prostate cancer growth through degradation of full-length and splice variant androgen receptors. Neoplasia. 2012; 14: 74-83.
18. Chan SC, Li Y, Dehm SM. Androgen receptor splice variants activate androgen receptor target genes and support aberrant prostate cancer cell growth independent of canonical androgen receptor nuclear localization signal. J.Biol.Chem. 2012; 287: 19736-49.
19. Hu R, Isaacs WB, Luo J. A snapshot of the expression signature of androgen receptor splicing variants and their distinctive transcriptional activities. Prostate. 2011; 71: 1656-67.
20. Watson PA, Chen YF, Balbas MD, Wongvipat J, Socci ND, Viale A, Kim K, Sawyers CL. Constitutively active androgen receptor splice variants expressed in castrationresistant prostate cancer require full-length androgen receptor. Proc.Natl.Acad.Sci.U.S.A. 2010; 107: 16759-65.
21. Zhan Y, Cao B, Qi Y, Liu S, Zhang Q, Zhou W, Xu D, Lu H, Sartor O, Kong W, Zhang H, Dong Y. Methylselenol prodrug enhances MDV3100 efficacy for treatment of castration-resistant prostate cancer. Int.J.Cancer. 2013; 133: 2225-33.
22. Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A, Wasielewska T, Welsbie D, Chen CD, Higano CS, Beer TM, Hung DT et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science. 2009; 324: 787-90.
23. Guo Z, Qiu Y. A new trick of an old molecule: androgen receptor splice variants taking the stage?! Int.J.Biol.Sci. 2011; 7: 815-22.
24. Balbas MD, Evans MJ, Hosfield DJ, Wongvipat J, Arora VK, Watson PA, Chen Y, Greene GL, Shen Y, Sawyers CL. Overcoming mutation-based resistance to antiandrogens with rational drug design. Elife. 2013; 2: e00499.
25. Korpal M, Korn JM, Gao X, Rakiec DP, Ruddy DA, Doshi S, Yuan J, Kovats SG, Kim S, Cooke VG, Monahan JE, Stegmeier F, Roberts TM, Sellers WR, Zhou W, Zhu P. An F876L Mutation in Androgen Receptor Confers Genetic and Phenotypic Resistance to MDV3100 (Enzalutamide). Cancer Discov. 2013; 3: 1030-43.
26. Joseph JD, Lu N, Qian J, Sensintaffar J, Shao G, Brigham D, Moon M, Maneval EC, Chen I, Darimont B, Hager JH. A Clinically Relevant Androgen Receptor Mutation Confers Resistance to Second-Generation Antiandrogens Enzalutamide and ARN-509. Cancer Discov. 2013; 3: 1020-9.
27. Arora VK, Schenkein E, Murali R, Subudhi SK, Wongvipat J, Balbas MD, Shah N, Cai L, Efstathiou E, Logothetis C, Zheng D, Sawyers CL. Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade. Cell. 2013; 155: 1309-22.
28. Li Y, Hwang TH, Oseth LA, Hauge A, Vessella RL, Schmechel SC, Hirsch B, Beckman KB, Silverstein KA, Dehm SM. AR intragenic deletions linked to androgen receptor splice variant expression and activity in models of prostate cancer progression. Oncogene. 2012; 31: 4759-67.
29. Nyquist MD, Li Y, Hwang TH, Manlove LS, Vessella RL, Silverstein KA, Voytas DF, Dehm SM. TALEN-engineered AR gene rearrangements reveal endocrine uncoupling of androgen receptor in prostate cancer. Proc.Natl.Acad. Sci.U.S.A. 2013; 110: 17492-7.
30. Centenera MM, Harris JM, Tilley WD, Butler LM. Minireview: The Contribution of Different Androgen Receptor Domains to Receptor Dimerization and Signaling. Mol Endocrinol. 2008; 22: 2373-82.
31. Andersen RJ, Mawji NR, Wang J, Wang G, Haile S, Myung JK, Watt K, Tam T, Yang YC, Banuelos CA, Williams DE, McEwan IJ, Wang Y, Sadar MD. Regression of Castrate- Recurrent Prostate Cancer by a Small-Molecule Inhibitor of the Amino-Terminus Domain of the Androgen Receptor. Cancer Cell. 2010; 17: 535-46.
32. Cao B, Liu X, Li J, Liu S, Qi Y, Xiong Z, Zhang A, Wiese T, Fu X, Gu J, Rennie PS, Sartor O, Lee BR, Ip C, Zhao L, Zhang H et al. 20(S)-protopanaxadiol-aglycone downregulation of the full-length and splice variants of androgen receptor. Int.J.Cancer. 2013; 132: 1277-87.
33. Li J, Cao B, Liu X, Fu X, Xiong Z, Chen L, Sartor O, Dong Y, Zhang H. Berberine Suppresses Androgen Receptor Signaling in Prostate Cancer. Molecular Cancer Therapeutics. 2011; 10: 1346-56.
34. Li X, Liu Z, Xu X, Blair CA, Sun Z, Xie J, Lilly MB, Zi X. Kava components down-regulate expression of AR and AR splice variants and reduce growth in patient-derived prostate cancer xenografts in mice. PLoS One. 2012; 7: e31213.
35. Mashima T, Okabe S, Seimiya H. Pharmacological targeting of constitutively active truncated androgen receptor by nigericin and suppression of hormone-refractory prostate cancer cell growth. Mol.Pharmacol. 2010; 78: 846-54.
36. Dong Y, Lee SO, Zhang H, Marshall J, Gao AC, Ip C. Prostate specific antigen expression is down-regulated by selenium through disruption of androgen receptor signaling. Cancer Res. 2004; 64: 19-22.
37. Furlan-Magaril M, Rincón-Arano Hc, Recillas-Targa F. Sequential Chromatin Immunoprecipitation Protocol: ChIPreChIP. DNA-Protein Interactions (543 edition) 2008: 253- 66.
38. Wang Q, Li W, Zhang Y, Yuan X, Xu K, Yu J, Chen Z, Beroukhim R, Wang H, Lupien M, Wu T, Regan MM, Meyer CA, Carroll JS, Manrai AK, Janne OA et al. Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer. Cell. 2009; 138: 245-56.
39. Gleave ME, Hsieh JT, Wu HC, von Eschenbach AC, Chung LW. Serum prostate specific antigen levels in mice bearing human prostate LNCaP tumors are determined by tumor volume and endocrine and growth factors. Cancer Res. 1992; 52: 1598-605.