Mitogen-activated protein kinase pathway is involved in α6 integrin gene expression in androgen-independent prostate cancer cells:: role of proximal Sp1 consensus sequence

Metastatic diseases of prostate cancer reveal high expression of alpha6 integrin and the activation of mitogen-activated protein kinases (MAP kinase). Therefore, the present study was conducted to examine whether MAP kinase pathway is involved in the alpha6 integrin gene expression in androgen-independent prostate cancer cell lines. alpha6 integrin mRNA expression, the alpha6 integrin promoter-induced luciferase activities and MAP kinase enzyme activities in androgen-independent LNCaP and PC-3 cell lines were higher than those in androgen-dependent LNCaP. Deletion and mutation analysis showed that Spl consensus sequence at -48 to -43 bp from the transcription start site was necessary for basal promoter activity. Binding of Spl to its consensus sequence in three cell lines was confirmed by electrophoretic mobility shift assays. Spl binding to its consensus sequence, as well as promoter activity and mRNA expression, were found to be inhibited by an inhibitor of MAP kinase kinase 1 and 2, U0126, in the androgen-independent cell lines. Our results indicate that the proximal Spl is necessary for basal promoter activity of the alpha6 integrin, suggesting that signal transduction from MAP kinases Co activation of Spl might be involved in a6 integrin gene expression in androgen-independent prostate cancer cell lines. (C) 2001 Elsevier Science B.V. Ah rights reserved.