Role of TMPRSS4 Modulation in Breast Cancer Cell Proliferation

Document Type: Research Articles

Authors

1 Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, China.

2 Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China.

3 University of Abomey Calavi, BP 526, Cotonou, Benin.

Abstract

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

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