Post-transcriptional and post-translational regulation of PTEN by transforming growth factor-β1

✍ Scribed by Yong Yang; Feng Zhou; Zengyu Fang; Liying Wang; Zengxia Li; Lidong Sun; Can Wang; Wantong Yao; Xiumei Cai; Jiawei Jin; Xiliang Zha

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 351 KB
• Volume: 106
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.22100

✦ Synopsis

Abstract

PTEN is a critical tumor suppressor gene mutated frequently in various human cancers. Previous studies have showed that PTEN mRNA expression is down‐regulated by TGF‐β1 in various cell lines. In present study, we have found that TGF‐β1 down‐regulates PTEN mRNA and protein expression in a dose‐ and time‐dependent manner in hepatocarcinoma cell line SMMC‐7721. Based on the PTEN promoter dual‐luciferase report assay, we have found that PTEN transcription is not affected by TGF‐β1. By using transcriptional inhibitor actinomycin D (Act D), the turnover rate of PTEN transcripts appeared to be accelerated during TGF‐β1 stimulation, which indicated that down‐regulation of PTEN by TGF‐β1 was post‐transcriptional. What interested us was that transfection of PTEN coding sequence increased TGF‐β1‐induced degradation of PTEN mRNA, suggesting that PTEN coding region was account for TGF‐β1‐mediated down‐regulation of PTEN. In addition, TGF‐β1 down‐regulated PTEN expression was blocked by the TβIR inhibitor SB431542 and the p38 inhibitor SB203580, suggesting Smad and p38 MAPK signal pathways played crucial roles in PTEN down‐regulation via TGF‐β1 stimulation. In this study, we also found TGF‐β1 accelerated down‐regulation of PTEN through the ubiquitin‐proteasome pathway. Collectively, our data clearly demonstrated that TGF‐β1‐mediated down‐regulation of PTEN was post‐transcriptional and post‐translational, depending on its coding sequence, Smad and p38‐MAPK signal pathways were involved in this down‐regulation. J. Cell. Biochem. 106: 1102–1112, 2009. © 2009 Wiley‐Liss, Inc.