TMEPAI/PMEPA1 enhances tumorigenic activities in lung cancer cells.
Bottom Line: These results suggest that constitutive expression of TMEPAI in these cancer cells depends on autocrine TGF-β stimulation.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: To examine the effects of TMEPAI on the metastatic potential in lungs, we injected Calu3-sh#9 and Calu3-sh#10 cells into the tail veins of NOD-SCID mice. Eight weeks after injection, mice were killed and the collected lungs were examined histopathologically with H&E staining. We also stained for Ki-67 to detect proliferating cancer cells. Using morphometric software, we calculated the percentage of the representative tumor areas in the total lung areas. Calu3-sh#9 and Calu3-sh#10 cells formed significantly smaller tumors both is size and numbers than those of the control Calu3 cells (Fig.6). These results indicated that knockdown of TMEPAI suppresses the ability of lung cancer cells to develop metastatic tumors in lungs.
Affiliation: Department of Experimental Pathology, Graduate School of Comprehensive Human Sciences and Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.