title: Effect and mechanism of the metastasis suppressor gene BRMS1 on the migration of breast cancer cells.
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-(32)P) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325000, People's Republic of China.
authors.forename: Yin-Long
authors.initials: YL
authors.lastname: Yang
authors.forename: Cheng-Ze
authors.initials: CZ
authors.lastname: Chen
authors.forename: Lang-Ping
authors.initials: LP
authors.lastname: Jin
authors.forename: Qian-Qing
authors.initials: QQ
authors.lastname: Ji
authors.forename: Yi-Zuo
authors.initials: YZ
authors.lastname: Chen
authors.forename: Quan
authors.initials: Q
authors.lastname: Li
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Zhang
authors.forename: Jin-Miao
authors.initials: JM
authors.lastname: Qu
keywords: BRMS1; Breast cancer; G protein; cAMP; connexin; metastasis; migration