Increased expression of integrin β1 subunit enhances p21WAF1/Cip1 transcription through the Sp1 sites and p300-mediated histone acetylation in human hepatocellular carcinoma cells
✍ Scribed by Zhengyu Fang; Yi Fu; Yulong Liang; Zengxia Li; Wen Zhang; Jiawei Jin; Yong Yang; Xiliang Zha
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 276 KB
- Volume
- 101
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Abstract
Integrins, a class of membrane receptors, are major players in transmitting the mechanical force across the plasma membrane. We previously reported that overexpression of integrin β1 subunit imposed a growth inhibitory effect on the hepatocellular carcinoma cell line SMMC‐7721 through transcriptional activation of p21^WAF1/CIP1^ gene. In this study, we further determined the molecular mechanisms underlying p21^WAF1/CIP1^ expression induced by integrin β1 overexpression. We report herein that overexpression of integrin β1 subunit upregulates p21^WAF1/Cip1^ transcription through a p53‐independent pathway. The overexpressed integrin β1 activates the p21^WAF1/Cip1^ promoter through the Sp1/Sp3 sites and makes more transcription factor Sp1 recruited to the proximal p21 promoter region. In addition, it makes the acetylation value of histone proteins increased across some parts of the p21^WAF1/Cip1^ gene, especially in the promoter region. The transcriptional co‐activator p300, which possesses intrinsic histone acetyltransferase, was found to be involved in the integrin β1‐mediated histone acetylation and p21 transcriptional activation. Therefore, these findings presented the mechanisms by which integrin β1 induced the elevated p21 expression in hepatic cancer cells. J. Cell. Biochem. 101: 654–664, 2007. © 2007 Wiley‐Liss, Inc.