Role of TMPRSS4 Modulation in Breast Cancer Cell Proliferation.

Ganiou Assani,Fuxiang Zhou,Yudi Xiong,Akadiri Yessoufou,Yunfeng Zhou,Xiaoyuan Yu,Julien Segbo

doi:10.31557/apjcp.2019.20.6.1849

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.

Highlights

Breast cancer is the most common neoplasm diagnosis among women worldwide and is the leading cause of female cancer death (Jemal et al, 2011)
Regarding the effect of TMPRSS4 on cancer cell cycle, our results showed that TMPRSS4 silencing in MDA-MB-468 breast cancer promotes the cell cycle arrest in G2/M phase associated to the reduction of the cell cycle arrest in S phase while induction of the TMPRSS4 overexpression in MCF-7 breast cancer cell has no significant effect on cell cycle process
P53 induces the expression of p21WAF1/CIT1/Sdi1, an inhibitor of the cyclin-dependent kinases (CDKs)2,3,4 and 6 (Shaw et al, 1996).This suggested that the expression of ER in the MCF-7 cell may lead to the lack of the p53 and unchanged of cell cycle process by TMPRSS4

Summary

Introduction

Breast cancer is the most common neoplasm diagnosis among women worldwide and is the leading cause of female cancer death (Jemal et al, 2011). TTPs are implicated in the regulation of cellular signaling, tumor initiation, and progression via itself deregulation (Netzel Arnett et al, 2003; Hooper et al, 2001; Choi et al.,2009 ). Loss of telomere protection ( telomere maintenance) activates DNA damage like signaling response which can halt cell proliferation or promote cell death via induction of. 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). 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

Methods

Results

Conclusion