Understanding the Mechanism of Action of Breast Metastasis

Abstract

The focus of this study is to understand the biology behind the metastasis suppression via BRMS1, a recently identified metastasis suppressor gene. BRMS1 is a protein with a glutamic acid rich N-terminus, coiled-coil domain, an imperfect leucine zipper and nuclear localization signals. It is expressed almost ubiquitously in human tissues and is highly conserved across species. Sub-cellular fractionation and fluorescence immuno-cytochemistry has indicated that it localizes to nucleus. BRMS1 is shown to restore homotypic gap-junctional communication. Our hypothesis is that it may be involved in transcription regulatory complex. To identify proteins that interacting with BRMS1 a yeast two-hybrid screen was performed using full length BRMS1 as a bait and human mammary gland library as a prey. We confirmed RBP1 (Rb binding protein), FLJ00052 (EST), MRJ (Hsp40 related chaperon) and Nmi (N-myc interactor) as potential interactors at cellular level by co-immunoprecipitation studies. We have further demonstrated that BRMS1 is a component of mSin3-HDAC complex. Based on these observations it is tempting to speculate that BRMS1 regulates gene expression by histone deacetylation. Currently we are studying the role of this complex in regulation of metastasis of breast cancer.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2005
Accession Number
ADA442721

Entities

People

  • Rajeev S Samant

Organizations

  • University of Alabama

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Biochemistry
  • Biological Therapy
  • Breast Cancer
  • Carrier Proteins
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Enzyme Inhibitors
  • Gene Expression
  • Genetics
  • Health Services
  • Mammary Glands
  • Molecular Biology
  • Neoplasms
  • Proteins

Fields of Study

  • Biology

Readers

  • Military Engineering.
  • Molecular Biology and Genetics
  • Molecular and Cellular Biochemistry