A New Trick of an Old Molecule: Androgen Receptor Splice Variants Taking the Stage?!

Overview

Journal Int J Biol Sci

Specialty Biology

Date 2011 Jul 14

PMID 21750650

Citations 36

Authors

Zhiyong Guo

Yun Qiu

Affiliations

Soon will be listed here.

Abstract

Prostate cancer is the second leading cause of cancer-related death in American men. Although most prostate cancers are initially androgen-dependent and respond to androgen ablation therapy, majority of them eventually relapse and progress into incurable castration-resistant (or hormone refractory) prostate cancer. The underlying mechanisms are the focus of intensive investigation for development of more effective treatment. Mounting evidence from both clinical and basic research has demonstrated that the activity of the androgen receptor (AR) is still required for castration-resistant prostate cancer. Multiple mechanisms by which AR is re-activated under androgen-depleted conditions may be involved in the development of castration resistance. The recent identification of AR splicing variants may add another layer of complexity in AR biology. The present review summarizes recent progress in study of AR splicing variants in prostate cancer.

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References

Gelmann E . Molecular biology of the androgen receptor. J Clin Oncol. 2002; 20(13):3001-15. DOI: 10.1200/JCO.2002.10.018. View

Chang C, Kokontis J, Liao S . Molecular cloning of human and rat complementary DNA encoding androgen receptors. Science. 1988; 240(4850):324-6. DOI: 10.1126/science.3353726. View

Li Y, Alsagabi M, Fan D, Bova G, Tewfik A, Dehm S . Intragenic rearrangement and altered RNA splicing of the androgen receptor in a cell-based model of prostate cancer progression. Cancer Res. 2011; 71(6):2108-17. PMC: 3059379. DOI: 10.1158/0008-5472.CAN-10-1998. View

Heinlein C, Chang C . Androgen receptor in prostate cancer. Endocr Rev. 2004; 25(2):276-308. DOI: 10.1210/er.2002-0032. View

Culig Z, Hobisch A, Bartsch G, Klocker H . Androgen receptor--an update of mechanisms of action in prostate cancer. Urol Res. 2000; 28(4):211-9. DOI: 10.1007/s002400000111. View

Guo Z, Yang X, Sun F, Jiang R, Linn D, Chen H . A novel androgen receptor splice variant is up-regulated during prostate cancer progression and promotes androgen depletion-resistant growth. Cancer Res. 2009; 69(6):2305-13. PMC: 2672822. DOI: 10.1158/0008-5472.CAN-08-3795. View

Gregory C, He B, Wilson E . The putative androgen receptor-A form results from in vitro proteolysis. J Mol Endocrinol. 2001; 27(3):309-19. DOI: 10.1677/jme.0.0270309. View

Jemal A, Siegel R, Xu J, Ward E . Cancer statistics, 2010. CA Cancer J Clin. 2010; 60(5):277-300. DOI: 10.3322/caac.20073. View

Sun S, Sprenger C, Vessella R, Haugk K, Soriano K, Mostaghel E . Castration resistance in human prostate cancer is conferred by a frequently occurring androgen receptor splice variant. J Clin Invest. 2010; 120(8):2715-30. PMC: 2912187. DOI: 10.1172/JCI41824. View

10.

Watson P, Chen Y, Balbas M, Wongvipat J, Socci N, Viale A . Constitutively active androgen receptor splice variants expressed in castration-resistant prostate cancer require full-length androgen receptor. Proc Natl Acad Sci U S A. 2010; 107(39):16759-65. PMC: 2947883. DOI: 10.1073/pnas.1012443107. View

11.

Culig Z, Klocker H, Bartsch G, Hobisch A . Androgen receptors in prostate cancer. Endocr Relat Cancer. 2002; 9(3):155-70. DOI: 10.1677/erc.0.0090155. View

12.

Feldman B, Feldman D . The development of androgen-independent prostate cancer. Nat Rev Cancer. 2002; 1(1):34-45. DOI: 10.1038/35094009. View

13.

Lubahn D, Joseph D, Sullivan P, Willard H, French F, Wilson E . Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Science. 1988; 240(4850):327-30. DOI: 10.1126/science.3353727. View

14.

Wilson C, McPhaul M . A and B forms of the androgen receptor are present in human genital skin fibroblasts. Proc Natl Acad Sci U S A. 1994; 91(4):1234-8. PMC: 43131. DOI: 10.1073/pnas.91.4.1234. View

15.

Rundlett S, Wu X, Miesfeld R . Functional characterizations of the androgen receptor confirm that the molecular basis of androgen action is transcriptional regulation. Mol Endocrinol. 1990; 4(5):708-14. DOI: 10.1210/mend-4-5-708. View

16.

Hu R, Dunn T, Wei S, Isharwal S, Veltri R, Humphreys E . Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate cancer. Cancer Res. 2009; 69(1):16-22. PMC: 2614301. DOI: 10.1158/0008-5472.CAN-08-2764. View

17.

Marcelli M, Cunningham G . Hormonal signaling in prostatic hyperplasia and neoplasia. J Clin Endocrinol Metab. 1999; 84(10):3463-8. DOI: 10.1210/jcem.84.10.6083. View

18.

Tepper C, Boucher D, Ryan P, Ma A, Xia L, Lee L . Characterization of a novel androgen receptor mutation in a relapsed CWR22 prostate cancer xenograft and cell line. Cancer Res. 2002; 62(22):6606-14. View

19.

Cutress M, Whitaker H, Mills I, Stewart M, Neal D . Structural basis for the nuclear import of the human androgen receptor. J Cell Sci. 2008; 121(Pt 7):957-68. DOI: 10.1242/jcs.022103. View

20.

Goldstein A, Huang J, Guo C, Garraway I, Witte O . Identification of a cell of origin for human prostate cancer. Science. 2010; 329(5991):568-71. PMC: 2917982. DOI: 10.1126/science.1189992. View