雄激素受体突变体T877A的促细胞增殖效应

目的　评价雄激素受体突变体 (mtAR)对细胞生长的促进作用。方法　我们利用三种重组腺病毒即野生型雄激素受体 (Ad wtAR)、一个被广泛研究的前列腺癌 (CaP)相关的mtAR(Ad mtAR ,T877A)、以及作为对照的腺病毒载体 ,评价并比较了野生型AR及mtAR的促细胞生长效应。结果　相对于被野生型或者对照的腺病毒转染的LNCaP、PC3细胞 ,转染mtAR的LNCaP、PC3细胞无论有无合成的雄激素 (R1881)存在的情况下均显示出更强的细胞增殖作用。并且用重组T877A腺病毒转染的LNCaP和PC3细胞显示了对R1881更强的反应性。结论　这些发现提出了崭新的关于mtAR在CaP细胞中作用的细胞生物学方面的见解 ,并且表明mtAR(T877A)可能为前列腺癌病程的进展提供了选择性的细胞生长的效应。

Promotion of cell growth by mutant androgen receptor T877A

Objective To evaluate the cell growth promoting effects of mutant androgen receptor (mtAR). Methods By using adenovirus expression vectors of the wild type AR (Ad-wtAR), a widely studied prostate cancer (CaP) associated mtAR (Ad-mtAR, T877A), and the control adenovirus vector (Ad-control), we evaluated and compared cell biologic effects of wtAR and mtAR. Results In comparison to the Ad-wtAR or Ad-control infected LNCaP and PC3 cells, Ad-mtAR (T877A) infected LNCaP and PC3 cells exhibited enhanced cell growth in the presence or absence of synthetic androgen R1881. Furthermore, Ad-mtAR (T877A) infected LNCaP and PC3 cells showed increased androgen responsiveness to R1881. Conclusion These findings provide novel cell biologic insights into effects of the AR mutations in CaP cells and suggest that mtARs with properties of AR (T877A) may provide selective cell growth advantage in the progression of CaP.