Transforming growth factor-β1 and lysophosphatidic acid activate integrin β6 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 Itg beta 6 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.