PC‐3 cells with enhanced androgen receptor signaling: A model for clonal selection in prostate cancer
- 5 March 2004
- journal article
- research article
- Published by Wiley in The Prostate
- Vol. 60 (4) , 352-366
- https://doi.org/10.1002/pros.20079
Abstract
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‐3AR− 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‐3AR− 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‐3AR− 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‐3AR− 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.Keywords
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