INTRODUCTION: Prostate cancer cells can switch from an androgen-dependent state to an androgen-independent state after a continuous androgen ablation therapy. However, the molecular mechanisms underlying this switch are still unclear. Therefore, we explored the change in androgen receptor (AR)-related gene expression during this transition in a novel cell model. MATERIAL AND METHODS: Prostate cancer cells were continuously treated with competitive androgen receptor inhibitor hydroxyflutamide for 1.5 years, which yielded an flutamide-insensitive LNCaP subline, LNCaP-flu, as confirmed by MTT assays, flow cytometry, and electron microscopy. We analyzed the differences in gene expression in LNCaP-flu cells and LNCaP cells using gene chips and follow-up RT-PCR. RESULTS: Over 2,428 genes were differentially expressed between these cell lines: 1,194 were down-regulated and 1,234 were up-regulated. Three genes in particular were considered related to the androgen-dependent transition: NCOR1, TIF2 (NCOA2), and ARA70 (NCOA4). There were no apparent changes in expression of the androgen receptor or prostate-specific antigen. CONCLUSION: ARs and associated coregulators play a central role in the flutamide-insensitive transition of prostate cancer cells. Although AR expression does not change during this transition, the change in AR coregulators may be a critical factor in the development of antiandrogen insensitivity.
INTRODUCTION:Prostate cancer cells can switch from an androgen-dependent state to an androgen-independent state after a continuous androgen ablation therapy. However, the molecular mechanisms underlying this switch are still unclear. Therefore, we explored the change in androgen receptor (AR)-related gene expression during this transition in a novel cell model. MATERIAL AND METHODS:Prostate cancer cells were continuously treated with competitive androgen receptor inhibitor hydroxyflutamide for 1.5 years, which yielded an flutamide-insensitive LNCaP subline, LNCaP-flu, as confirmed by MTT assays, flow cytometry, and electron microscopy. We analyzed the differences in gene expression in LNCaP-flu cells and LNCaP cells using gene chips and follow-up RT-PCR. RESULTS: Over 2,428 genes were differentially expressed between these cell lines: 1,194 were down-regulated and 1,234 were up-regulated. Three genes in particular were considered related to the androgen-dependent transition: NCOR1, TIF2 (NCOA2), and ARA70 (NCOA4). There were no apparent changes in expression of the androgen receptor or prostate-specific antigen. CONCLUSION: ARs and associated coregulators play a central role in the flutamide-insensitive transition of prostate cancer cells. Although AR expression does not change during this transition, the change in AR coregulators may be a critical factor in the development of antiandrogen insensitivity.
Authors: F Herranz Amo; F Arias Funez; M Arrizabalaga Moreno; F J Calahorra Fernández; J Carballido Rodríguez; R Diz Rodríguez; J A Herrero Payo; C Llorente Abarca; J C Martín Martínez; L Martínez-Piñeiro Lorenzo; R Mínguez Martínez; J Moreno Sierra; A Rodríguez Antolín; J C Tamayo Ruiz; J Turo Antona Journal: Actas Urol Esp Date: 2003-05 Impact factor: 0.994
Authors: Michael F Leitzmann; Elizabeth A Platz; Meir J Stampfer; Walter C Willett; Edward Giovannucci Journal: JAMA Date: 2004-04-07 Impact factor: 56.272