IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
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Int J Clin Exp Med 2013;6(10):908-916
Original Article
Effect and mechanism of the metastasis suppressor gene BRMS1 on the migration
of breast cancer cells
Yin-Long Yang, Cheng-Ze Chen, Lang-Ping Jin, Qian-Qing Ji, Yi-Zuo Chen, Quan Li, Xiao-Hua Zhang, Jin-Miao Qu
Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of
China. Equal contributors.
Received September 24, 2013; Accepted October 9, 2013; Epub October 25, 2013; Published October 30, 2013
Abstract: Objective: To study the effect of the transfected Breast cancer metastasis suppressor 1 (BRMS1) gene on the migration of
breast cancer cells and the possible mechanisms involved. Methods: MDA-MB-231HM cells which have a high propensity of
metastasize to lung was sieved from MDA-MB-231 and its derivative cells stable transfected with BRMS1 were used to study in vitro.
Cell migratory ability was observed. The cellular cyclic adenylic acid (cAMP) concentration was tested by radioimmunoassay (RIA). The
activity of adenylate cyclase (AC), phosphodiesterase (PDE) and protein kinase A (PKA) were measured by enzyme immunoassay (EIA)
and (γ-32P) ATP incorporation. The effect of BRMS1 on connexins (Cx) expression was analyzed by by RT-PCR and Western blot.
Results: Overexpression of BRMS1 significantly inhibited cell migration in MDA-MB-231HM cells in vitro. However, BRMS1’s effect on
cell migration could be eliminated after pretreating with pertussis toxin (PTX). BRMS1 overexpression increased cellular cAMP and PKA
activity by activating the activity of AC. Furthermore, BRMS1 overexpression up-regulated Cx26 expression, whereas Cx32, Cx43
expressions did not changed. Conclusion: The present study indicated G-protein-coupled cAMP signaling pathway was involved in
BRMS1 related MDA-MB-231HM cells migration, and BRMS1 could change connexins (Cx) expression profiles through increasing
expression of Cx26 in cells. (IJCEM1309026).
Keywords: Breast cancer, BRMS1, cAMP, migration, metastasis, G protein, connexin
Address correspondence to: Jin-Miao Qu, Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical
University, Wenzhou 325000, China. Tel: +86-0577-55579462; E-mail: docpanyf@aliyun.com
