Das Susobhan, Roth Cherice P, Wasson Lori M, Vishwanatha Jamboor K
Institute of Cancer Research and Department of Molecular Biology and Immunology, University of North Texas Health Science Center at Fort Worth, Texas 76107, USA.
Prostate. 2007 Oct 1;67(14):1550-64. doi: 10.1002/pros.20640.
Signal transducer and activator of transcription (STAT)-6 is a member of the STAT family of latent transcription factors. In this investigation, we examined STAT6 expression in clinical prostate cancer tissue specimen and determined its role in prostate cell proliferation and migration.
STAT6 expression in cell lines and tissues was analyzed by RT-PCR, IHC and/or immunoblot analyses. Down-regulation of STAT6 expression was achieved by STAT6 siRNA and its effect on cell migration and apoptosis was measured.
STAT6 is highly expressed in the fibromuscular stroma of prostate cancer specimens. STAT6 is also expressed in the malignant epithelial layer and prostate intraepithelial neoplasia (PIN). STAT6 expression was significantly correlated with high histological grades of prostate cancer as well as with tumor size. Our data indicate deregulated STAT6 mRNA and protein expression in prostate cancer cells with high levels in the non-cancerous HPV 18C-1 and cancerous DU145 cell lines and low levels in PC3 and LNCaP cells. Phosphorylated STAT6 was expressed in all three cancer cell lines DU145, PC3, and LNCaP. Down-regulation of STAT6 using siRNA leads to the induction of early apoptosis in DU145 cells and inhibits migration of these cells. Significant reduction in cell viability and transcriptional down-regulation of the anti-apoptotic protein Bcl-X(L) was observed followed by STAT6 down-regulation in DU145 cells. Interestingly STAT6 also regulates transcription of 15-lipoxygenase-1 gene in DU145 cells.
Our data suggest that STAT6 is a survival factor in prostate cancer and regulates the genetic transcriptional program that is responsible for prostate cancer progression.
信号转导及转录激活因子（STAT）-6是潜在转录因子STAT家族的成员。在本研究中，我们检测了STAT6在临床前列腺癌组织标本中的表达，并确定了其在前列腺细胞增殖和迁移中的作用。
通过逆转录聚合酶链反应（RT-PCR）、免疫组织化学（IHC）和/或免疫印迹分析来检测细胞系和组织中STAT6的表达。通过STAT6小干扰RNA（siRNA）下调STAT6表达，并检测其对细胞迁移和凋亡的影响。
STAT6在前列腺癌标本的纤维肌基质中高表达。STAT6也表达于恶性上皮层和前列腺上皮内瘤变（PIN）中。STAT6表达与前列腺癌的高组织学分级以及肿瘤大小显著相关。我们的数据表明，在前列腺癌细胞中STAT6 mRNA和蛋白表达失调，在非癌性人乳头瘤病毒18C-1和癌性DU145细胞系中水平较高，而在PC3和LNCaP细胞中水平较低。磷酸化的STAT6在所有三种癌细胞系DU145、PC3和LNCaP中均有表达。使用siRNA下调STAT6可导致DU145细胞早期凋亡的诱导，并抑制这些细胞的迁移。在DU145细胞中，STAT6下调后观察到细胞活力显著降低以及抗凋亡蛋白Bcl-X(L)的转录下调。有趣的是，STAT6还调节DU145细胞中15-脂氧合酶-1基因的转录。
我们的数据表明，STAT6是前列腺癌中的一种生存因子，并调节负责前列腺癌进展的基因转录程序。
