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
Related in: MedlinePlus
Mentions: The TFPI-2 gene was methylated in several lung cancer cell lines, including NCI-H358, NCI-H520, and NCI-H1975 (Fig.5b). When these cells were treated with the methylation inhibitor 5-aza-2′-deoxycytidine (5 μM) or the histone deacetylase inhibitor TSA (0.5 μM), the methylation level of TFPI-2 decreased and the mRNA expression level of TFPI-2 dramatically increased (Fig.5c,d). Conversely, these inhibitors reduced TMPRSS4 expression (Fig.5e). Finally, these agents inhibited the growth of these cell lines (Fig.6).
Affiliation: Department of Pulmonary Medicine, School of Medicine, Keio University, Tokyo, Japan.