Androgen receptor expression is regulated by the phosphoinositide 3-kinase/Akt pathway in normal and tumoral epithelial cells
Androgen receptor expression is regulated by the phosphoinositide 3-kinase/Akt pathway in normal and tumoral epithelial cells
复制标题
DOI：
10.1042/bj20020585
复制
发表时间：
2002-09-15
影响因子：
4.1
通讯作者：
Morel, L
中科院分区：
文献类型：
--
作者：
Manin, M;Baron, S;Morel, L
雄激素受体（AR）是一种配体反应性转录因子，已知在前列腺癌的发病机制中发挥核心作用。然而，AR基因在正常和病理前列腺中的表达调控仍然知之甚少。本研究的重点是磷脂酰肌醇3-激酶（PI 3-激酶）/Akt轴对输精管上皮细胞（VDEC）和LNCaP细胞（来源于确诊为转移性前列腺癌的50岁患者左锁骨上淋巴结转移）中AR表达的影响，VDEC是研究雄激素调节基因表达的合适模型。综上所述，我们的数据首次表明，PI 3-激酶/Akt途径是基础和二氢睾酮诱导的AR蛋白在VDEC和LNCaP中表达所必需的。PI 3-激酶/Akt通路的抑制降低了AR表达，并且AR蛋白水平的下降与VDEC中AR mRNA的减少相关，但在LNCaP中不相关。由于PI 3-激酶/Akt轴在前列腺癌中是活跃的，PI 3-激酶/Akt和AR信号通路之间的串扰可能对内分泌治疗有意义。
The androgen receptor (AR) is a ligand-responsive transcription factor known to play a central role in the pathogenesis of prostate cancer. However, the regulation of AR gene expression in the normal and pathological prostate remains poorly understood. This study focuses on the effect of the phosphomositide 3-kinase (PI 3-kinase)/Akt axis on AR expression in vas deferens epithelial cells (VDEC), a suitable model to study androgen regulation of gene expression, and LNCaP cells (derived from a metastasis at the left supraclavicular lymph node from a 50-year-old patient with a confirmed diagnosis of metastatic prostate carcinoma). Taken together, our data show for the first time that the PI 3-kinase/Akt pathway is required for basal and dihydrotestosterone-induced AR protein expression in both VDEC and LNCaP. Inhibition of the PI 3-kinase/Akt pathway reduced AR expression and the decline in AR protein level correlated with a decrease in AR mRNA in VDEC but not in LNCaP. Since PI 3-kinase/Akt axis is active in prostate cancer, cross-talk between PI 3-kinase/Akt and AR signalling pathways may have implications for endocrine therapy.