Transforming growth factor-[beta]1 and lysophosphatidic acid activate integrin [beta]6 gene promoter in Hep-3B cells

Although it is difficult to detect [alpha]v[beta]6 integrin ([alpha]v[beta]6) in normal epithelia cells, its expression is upregulated during wound healing and carcinogenesis. Overexpression of [alpha]v[beta]6 has been demonstrated in epithelial cell carcinomas, such as adenocarcinoma of the colon and ovary. However, the expression of [alpha]v[beta]6 has not been reported in hepatocellular carcinoma (HCC). We previously indicated that LPA may induce [alpha]v[beta]6-mediated TGF-[beta]1 signaling mechanisms during the pathogenesis of lung injury and fibrosis. In addition, transforming growth factor-[beta]1 (TGF-[beta]1) and lysophosphatidic acid (LPA) have been demonstrated to participate in the progression of HCC. In the present study, we hypothesized that TGF-[beta]1 and LPA would serve a key role in the subunit integrin [beta]6 (Itg[beta]6) transcriptional regulatory mechanism in HCC. It was identified that human HCC tissues and Hep-3B cells expressed Itg[beta]6. Treatment of Hep-3B with TGF-[beta]1 or LPA increased the expression of Itg[beta]6. Furthermore, truncation experiments indicated a positive regulatory region at -326 to -157 bp of the ItgP6 promoter. TGF-[beta]1 and LPA increased transcriptional activation at this regulatory region. To the best of our knowledge, the present study was the first to demonstrate Itg[beta]6 expression in HCC, and the data indicate that TGF-[beta]1 and LPA regulate Itg[beta]6 expression through the Itg[beta]6 gene promoter, which is an important factor in the development of HCC.