Alternative titles; symbols
HGNC Approved Gene Symbol: BRMS1
Cytogenetic location: 11q13.2 Genomic coordinates (GRCh38) : 11:66,337,339-66,345,104 (from NCBI)
BRMS1 is a human breast carcinoma metastasis suppressor gene that maps to 11q13, a hotspot in breast cancer progression (Seraj et al., 2000).
There are several regions spanning the long arm of chromosome 11 for which associations have been made with progression of breast cancer (114480). Among the most common changes are amplification and deletion involving regions near band 11q13. Deletions involving 11q13-q14 are observed in high frequency in late-stage, metastatic breast carcinomas. This prompted Phillips et al. (1996) to introduce a normal human chromosome 11 into metastatic human breast carcinoma cells. They observed suppression of metastasis that did not affect tumorigenicity. Seraj et al. (2000) described the isolation and functional characterization of a full-length cDNA corresponding to a novel gene designated 'breast cancer metastasis suppressor 1' (BRMS1) from this region. The BRMS1 gene encodes a protein of 246 amino acids. Northern blot analysis detected variable expression of a 1.5-kb transcript in all tissues tested.
Hurst et al. (2008) stated that the BRMS1 protein contains an N-terminal, glutamine-rich domain, followed by 2 coiled-coil domains, and 2 C-terminal nuclear localization signals.
The BRMS1 gene is organized as 10 exons spanning approximately 10 kb (Seraj et al., 2000). Exon 1 is untranslated.
By fluorescence in situ hybridization, Seraj et al. (2000) mapped the BRMS1 gene to 11q13.1-q13.2.
To assess the effect of BRMS1 on breast carcinoma biologic behavior, Seraj et al. (2000) transfected BRMS1 into 2 independently derived metastatic human breast carcinoma cell lines. Stably transfected breast carcinoma cells still formed progressively growing, locally invasive tumors when injected into mammary fat pads, but were significantly less metastatic to lungs and regional lymph nodes.
Hurst et al. (2008) stated that BRMS1 interacts with ARID4A (180201) as part of SIN3-histone deacetylase chromatin remodeling complexes. Yeast 2-hybrid analysis showed that the second coiled-coil domain of BRMS1 interacted directly with ARID4A and an L174D point mutation in the second coiled-coil domain abolished the interaction. Coimmunoprecipitation analysis of human breast cancer cell lines expressing these BRMS1 mutations suggested an indirect association between mutant BRMS1 and ARID4A remained intact. Deletion of the first coiled-coil domain of BRMS1 abolished the indirect interaction. The BRMS1 L174D point mutation also impaired suppression of basal transcription by BRMS1/ARID4A, but it did not alter BRMS1-mediated suppression of metastasis.
Hurst, D. R., Xie, Y., Vaidya, K. S., Mehta, A., Moore, B. P., Accavitti-Loper, M. A., Samant, R. S., Saxena, R., Silveira, A. C., Welch, D. R. Alterations of BRMS1-ARID4A interaction modify gene expression but still suppress metastasis in human breast cancer cells. J. Biol. Chem. 283: 7438-7444, 2008. [PubMed: 18211900] [Full Text: https://doi.org/10.1074/jbc.M709446200]
Phillips, K. K., Welch, D. R., Miele, M. E., Lee, J. H., Wei, L. L., Weissman, B. E. Suppression of MDA-MB-435 breast carcinoma cell metastasis following the introduction of human chromosome 11. Cancer Res. 56: 1222-1227, 1996. [PubMed: 8640802]
Seraj, M. J., Samant, R. S., Verderame, M. F., Welch, D. R. Functional evidence for a novel human breast carcinoma metastasis suppressor, BRMS1, encoded at chromosome 11q13. Cancer Res. 60: 2764-2769, 2000. [PubMed: 10850410]