Transforming growth factor-β1 and lysophosphatidic acid activate integrin β6 gene promoter in hep-3B cells

Abstract

Although it is difficult to detect αvβ6 integrin (αvβ6) in normal epithelia cells, its expression is upregulated during wound healing and carcinogenesis. Overexpression of αvβ6 has been demonstrated in epithelial cell carcinomas, such as adenocarcinoma of the colon and ovary. However, the expression of αvβ6 has not been reported in hepatocellular carcinoma (HCC). We previously indicated that LPA may induce αvβ6-mediated TGF-β1 signaling mechanisms during the pathogenesis of lung injury and fibrosis. In addition, transforming growth factor-β1 (TGF-β1) and lysophosphatidic acid (LPA) have been demonstrated to participate in the progression of HCC. In the present study, we hypothesized that TGF-β1 and LPA would serve a key role in the subunit integrin β6 (Itgβ6) transcriptional regulatory mechanism in HCC. It was identified that human HCC tissues and Hep-3B cells expressed Itgβ6. Treatment of Hep-3B with TGF-β1 or LPA increased the expression of Itgβ6. Furthermore, truncation experiments indicated a positive regulatory region at-326 to-157 bp of the Itgβ6 promoter. TGF-β1 and LPA increased transcriptional activation at this regulatory region. To the best of our knowledge, the present study was the first to demonstrate Itgβ6 expression in HCC, and the data indicate that TGF-β1 and LPA regulate Itgβ6 expression through the Itgβ6 gene promoter, which is an important factor in the development of HCC.