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Mol Cancer. 2007 Jan 16;6:6.

Breast cancer metastasis suppressor 1 (BRMS1) inhibits osteopontin transcription by abrogating NF-kappaB activation.

Author information

1
Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama, USA. rsamant@usouthal.edu

Abstract

BACKGROUND:

Osteopontin (OPN), a secreted phosphoglycoprotein, has been strongly associated with tumor progression and aggressive cancers. MDA-MB-435 cells secrete very high levels of OPN. However metastasis-suppressed MDA-MB-435 cells, which were transfected with breast cancer metastasis suppressor 1 (BRMS1), expressed significantly less OPN. BRMS1 is a member of mSin3-HDAC transcription co-repressor complex and has been shown to suppress the metastasis of breast cancer and melanoma cells in animal models. Hence we hypothesized that BRMS1 regulates OPN expression.

RESULTS:

The search for a BRMS1-regulated site on the OPN promoter, using luciferase reporter assays of the promoter deletions, identified a novel NF-kappaB site (OPN/NF-kappaB). Electrophoretic mobility shift assays and chromatin immunoprecipitations (ChIP) confirmed this site to be an NF-kappaB-binding site. We also show a role of HDAC3 in suppression of OPN via OPN/NF-kappaB.

CONCLUSION:

Our results show that BRMS1 regulates OPN transcription by abrogating NF-kappaB activation. Thus, we identify OPN, a tumor-metastasis activator, as a crucial downstream target of BRMS1. Suppression of OPN may be one of the possible underlying mechanisms of BRMS1-dependent suppression of tumor metastasis.

PMID:
17227585
PMCID:
PMC1796551
DOI:
10.1186/1476-4598-6-6
[Indexed for MEDLINE]
Free PMC Article

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