Methylation-induced downregulation of TFPI-2 causes TMPRSS4 overexpression and contributes to oncogenesis in a subset of non-small-cell lung carcinoma.
Bottom Line: Interestingly, we found that TMPRSS4 expression was associated with tissue factor pathway inhibitor 2 (TFPI-2) expression in these clinical samples.Knockdown of TMPRSS4 reduced the proliferation rate in several lung cancer cell lines.We found a novel molecular mechanism that TFPI-2 negatively regulates cell growth by inhibiting transcription of TMPRSS4.
Affiliation: Department of Pulmonary Medicine, School of Medicine, Keio University, Tokyo, Japan.Show MeSH
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Mentions: The expression of TMPRSS4 and TFPI-2 was analyzed by immunohistochemistry in six cases (Fig.2). These cases included three ACs and three SCCs. TMPRSS4 was expressed mainly in the cell membrane and also in the cytoplasm of cancer cells, and TFPI-2 was expressed in the cytoplasm of cancer cells (Fig.2a). TMPRSS4 was not expressed in stromal cells, whereas TFPI-2 was expressed not only in cancer cells but also in elastic fiber and smooth muscle cells. Although the sample size was small and might not be representative of all cases, protein and mRNA expressions showed weak correlation for both genes (rs = 0.348 for TMPRSS4; rs = 0.395 for TFPI-2) (Fig.2b,c), and the protein expressions of these genes seemed to be negatively correlated (rs = −0.524) (Fig.2d).
Affiliation: Department of Pulmonary Medicine, School of Medicine, Keio University, Tokyo, Japan.