Role of TMPRSS4 Modulation in Breast Cancer Cell Proliferation

Abstract

Background: TMPRSS4 is a novel Type II transmembrane serine protease found at the surface of the cells and<br />is involved in the development and cancer progression. However, TMPRSS4 functions in breast cancer remain poor<br />understand. The present study investigated the function of TMPRSS4 in the breast cancer cells and the potential<br />mechanistic action underling. Materials and Methods: The lentiviral vectors causing TMPRSS4 down-regulation and<br />over-expression were established and transfected in MDA-MB-468 and MCF-7 cells, respectively. By using the CCK-<br />8 assay, cell proliferation was analyzed. Moreover, western blot was used to detect the expression of certain proteins<br />related to cell apoptosis (Bax and Bcl2) signaling pathway and telomere maintenance (POT1, TPP1, and UBE2D3).<br />Cell cycle and cell apoptosis were also analyzed by using the Flow cytometry analysis. TMPRSS4 expression was<br />detected at the mRNA level and protein level by performing qPCR and western blot technique, respectively. Results:<br />TMPRSS4 expression is inhibited in stable transfected MDA-MB-468-shTMPRSS4 cells compared to the control<br />MDA-MB-468-NC and its expression is up-regulated in stable transfected MCF-7-TMPTSS4 compared to its control<br />MCF-7-NC. Moreover, TMPRSS4 silencing in breast cancer reduces cells proliferation by promoting cell cycle arrest<br />in G2/M phase, cell apoptosis, and telomere maintenance impairment while the TMPRSS4 overexpression increases<br />cells proliferation through cell apoptosis reduction and telomere maintenance reinforcement associated with insignificant<br />change in cell cycle progression. Conclusion: TMPRSS4 plays important roles in cancer progression and may be<br />considered as a good therapeutic target for cancer gene therapy especially breast cancer.