BACKGROUND: Two sublines of the human prostate cancer cell line, PC-3, which is widely used as a model of prostate cancer progression, have been reported: PC-3(AR-) that do not express androgen receptor (AR), and PC-3AR+ that have measurable AR RNA but little protein. METHODS: We assayed the geneotype, karyotype, AR expression, and physical characteristics of the two PC-3 sublines, and compared their ability to elicit a transactivation response from ectopic AR in the presence and absence of specific AR coregulators. RESULTS: PC-3(AR-) and PC-3AR+ cells are genotypically and karyotypically similar, but exhibit salient differences in their morphology, growth rate, and expression of AR RNA. Whereas endogenous AR expression in PC-3AR+ cells does not result in sufficient protein to confer androgen responsiveness in culture, ectopic AR consistently elicited a much greater transactivation response in PC-3AR+ than in PC-3(AR-) cells, without altered sensitivity to activation by native ligand or AR coregulators including GRIP1, BRCA1, and Zac1. Moreover, phenotypic differences of AR variants implicated in prostate cancer susceptibility and progression were only observed in PC-3AR+ cells. Higher levels of known AR coregulator proteins detected in PC-3AR+ compared with PC-3(AR-) cells likely contribute to these differences. CONCLUSIONS: These studies provide new evidence that the androgen-signaling axis can be sensitized in prostate cancer cells, and have important implications for the analysis and interpretation of AR structure and function in in vitro cell systems.
BACKGROUND: Two sublines of the humanprostate cancer cell line, PC-3, which is widely used as a model of prostate cancer progression, have been reported: PC-3(AR-) that do not express androgen receptor (AR), and PC-3AR+ that have measurable AR RNA but little protein. METHODS: We assayed the geneotype, karyotype, AR expression, and physical characteristics of the two PC-3 sublines, and compared their ability to elicit a transactivation response from ectopic AR in the presence and absence of specific AR coregulators. RESULTS: PC-3(AR-) and PC-3AR+ cells are genotypically and karyotypically similar, but exhibit salient differences in their morphology, growth rate, and expression of AR RNA. Whereas endogenous AR expression in PC-3AR+ cells does not result in sufficient protein to confer androgen responsiveness in culture, ectopic AR consistently elicited a much greater transactivation response in PC-3AR+ than in PC-3(AR-) cells, without altered sensitivity to activation by native ligand or AR coregulators including GRIP1, BRCA1, and Zac1. Moreover, phenotypic differences of AR variants implicated in prostate cancer susceptibility and progression were only observed in PC-3AR+ cells. Higher levels of known AR coregulator proteins detected in PC-3AR+ compared with PC-3(AR-) cells likely contribute to these differences. CONCLUSIONS: These studies provide new evidence that the androgen-signaling axis can be sensitized in prostate cancer cells, and have important implications for the analysis and interpretation of AR structure and function in in vitro cell systems.
Authors: Grant Buchanan; Eleanor F Need; Jeffrey M Barrett; Tina Bianco-Miotto; Vanessa C Thompson; Lisa M Butler; Villis R Marshall; Wayne D Tilley; Gerhard A Coetzee Journal: Mol Cell Endocrinol Date: 2011-06-01 Impact factor: 4.102
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Authors: Nitin Patel; Tatsuo Itakura; Shinwu Jeong; Chun-Peng Liao; Pradip Roy-Burman; Ebrahim Zandi; Susan Groshen; Jacek Pinski; Gerhard A Coetzee; Mitchell E Gross; M Elizabeth Fini Journal: PLoS One Date: 2015-02-18 Impact factor: 3.240
Authors: Li Jia; Gilad Landan; Mark Pomerantz; Rami Jaschek; Paula Herman; David Reich; Chunli Yan; Omar Khalid; Phil Kantoff; William Oh; J Robert Manak; Benjamin P Berman; Brian E Henderson; Baruch Frenkel; Christopher A Haiman; Matthew Freedman; Amos Tanay; Gerhard A Coetzee Journal: PLoS Genet Date: 2009-08-14 Impact factor: 5.917