TMEPAI/PMEPA1 enhances tumorigenic activities in lung cancer cells.
Bottom Line: TMEPAI is constitutively and highly expressed in many types of cancer and is associated with poor prognosis.Knockdown of TMEPAI in Calu3 and NCI-H23 cells enhanced levels of Smad2 phosphorylation and significantly suppressed cell proliferation in the presence of TGF-β, indicating that highly expressed TMEPAI suppresses levels of Smad phosphorylation in these cancer cells and reduces the growth inhibitory effects of TGF-β/Smad signaling.Together, these experiments indicate that TMEPAI promotes tumorigenic activities in lung cancer cells.
Affiliation: Department of Experimental Pathology, Graduate School of Comprehensive Human Sciences and Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.Show MeSH
Related in: MedlinePlus
Mentions: The high expression levels of TMEPAI in lung cancer cells prompted us to examine how TMEPAI expression is constitutively enhanced in these cells. To investigate the possibility that TGF-β signaling is involved in TMEPAI expression, cells were treated with the TGF-β receptor kinase inhibitor SD208 or anti-TGF-β neutralizing antibodies. TMEPAI disappeared from all cell lines in the presence of SD208 (Fig.2a). Although the effects of the TGF-β neutralizing antibodies were not complete, they did cause the TMEPAI levels to significantly decrease to levels correlating with Smad2 phosphorylation levels in all three cell lines (Fig.2b). We further examined TGF-β activities in the conditioned media incubated 24 h with the lung cancer cells. Calu3 secreted abundant TGF-β in the culture media and it had positive correlation with the levels of TMEPAI expression (Fig.2c).
Affiliation: Department of Experimental Pathology, Graduate School of Comprehensive Human Sciences and Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.