Expression of the Breast Cancer Metastasis Suppressor 1 (BRMS1) maintains in vitro chemosensitivity of breast cancer cells

Cancer Lett. 2009 Aug 18;281(1):100-7. doi: 10.1016/j.canlet.2009.02.035.

Abstract

The Breast Cancer Metastasis Suppressor 1 (BRMS1) belongs to an expanding category of proteins called metastasis suppressors that demonstrate in vivo metastasis suppression while still allowing growth of the orthotopic tumor. Since BRMS1 decreases either the expression or function of multiple mediators implicated in resistance to chemotherapy (NF-kappaB, AKT, EGFR), we asked whether breast carcinoma cells expressing BRMS1 could be sensitized upon exposure to commonly used therapeutic agents that inhibit some of these same cellular mediators as BRMS1. In this report, we demonstrate that chemosensitivity of breast cancer cells is preserved in the presence of BRMS1. Further, BRMS1 does not change expression of AKT isoforms or PTEN, implicated in chemoresistance to common drug agents. Overall, our data with two different metastatic breast cancer cell lines indicates that BRMS1 expression status may not interfere with the response to commonly used chemotherapeutic agents in the management of solid tumors such as breast cancer. Since tumor protein expression analysis increasingly guides therapy decisions, our data may be of clinical benefit in disease management including profiling for BRMS1 expression before start of therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / pathology*
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / pathology*
  • Cell Division / drug effects
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / metabolism
  • Cell Line, Tumor / pathology
  • Doxorubicin / pharmacology
  • Drug Resistance, Neoplasm / genetics
  • Drug Resistance, Neoplasm / physiology*
  • Female
  • Fluorouracil / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • PTEN Phosphohydrolase / biosynthesis
  • PTEN Phosphohydrolase / genetics
  • Paclitaxel / pharmacology
  • Protein Isoforms / biosynthesis
  • Protein Isoforms / genetics
  • Proto-Oncogene Proteins c-akt / biosynthesis
  • Proto-Oncogene Proteins c-akt / genetics
  • Recombinant Fusion Proteins / physiology
  • Repressor Proteins
  • Tumor Stem Cell Assay
  • Vincristine / pharmacology

Substances

  • Antineoplastic Agents
  • BRMS1 protein, human
  • Neoplasm Proteins
  • Protein Isoforms
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Vincristine
  • Doxorubicin
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Paclitaxel
  • Fluorouracil