BRMS1 PROMOTER AND METASTATIC BREAST CANCER
BRMS1, a functional gene, is composed of 10 exons and ranged from 7.8kb of genomic DNA. It is a member of mSIN3-HDAC transcription co-repressor complex and resides normally in the nucleus. Product of alternative splicing, two mRNA transcripts, which are in turn translated into two distinct proteins, 246 amino acids and 290 amino acids. When the structure of BRMS1 promoter is studied, two hyper methylated cytosine-phosphoguanine (CpG) islands (region -3477 to -2214 and -531 to +608) are found. Hyper methylated CpG islands, mostly because of tightly packed nucleosomes, block BRMS1 activation. Blocking transcription factor binding can also inhibit gene expression. The function of BRMS1 (one of metastatic suppressor gene) is to inhibit metastasis of tumor without having any effect on primary tumor growth. It localizes in chromosome 11, which is in association with growth and spread of human breast cancer. BRMS1 blocks spread of breast cancer by binding with histone deacetylase complexes (HDAC) and aberrant gene regulation is the outcome of this interaction. NF-kB (nuclear factor kappa B), activated in many malignancies and important in apoptosis, is negatively regulated by BRMS1. Two hyper methylated CpG islands are found in BRMS1 …show more content…
Very high levels of OPN are seen in MDA-MB-435 cells. On the OPN promoter, NF-kB site is where BRMS1 regulation occurs. BRMS1 expression restricts IkBα phosphorylation and degradation, resulting in a decrease in p65 and p50 nuclear translocation. It is also involved in BF-kB acetylation. BRMS1 suppressed OPN at the RNA and protein level. It interacts with HDAC3, which deacetylates p65. This causes NF-kB inactivation, which reduces OPN expression. Reduction of OPN expression by BRMS1 is either due to decrease in p65 trans-activation or reduction in NF-kB binding to the OPN
BRMS1, a functional gene, is composed of 10 exons and ranged from 7.8kb of genomic DNA. It is a member of mSIN3-HDAC transcription co-repressor complex and resides normally in the nucleus. Product of alternative splicing, two mRNA transcripts, which are in turn translated into two distinct proteins, 246 amino acids and 290 amino acids. When the structure of BRMS1 promoter is studied, two hyper methylated cytosine-phosphoguanine (CpG) islands (region -3477 to -2214 and -531 to +608) are found. Hyper methylated CpG islands, mostly because of tightly packed nucleosomes, block BRMS1 activation. Blocking transcription factor binding can also inhibit gene expression. The function of BRMS1 (one of metastatic suppressor gene) is to inhibit metastasis of tumor without having any effect on primary tumor growth. It localizes in chromosome 11, which is in association with growth and spread of human breast cancer. BRMS1 blocks spread of breast cancer by binding with histone deacetylase complexes (HDAC) and aberrant gene regulation is the outcome of this interaction. NF-kB (nuclear factor kappa B), activated in many malignancies and important in apoptosis, is negatively regulated by BRMS1. Two hyper methylated CpG islands are found in BRMS1 …show more content…
Very high levels of OPN are seen in MDA-MB-435 cells. On the OPN promoter, NF-kB site is where BRMS1 regulation occurs. BRMS1 expression restricts IkBα phosphorylation and degradation, resulting in a decrease in p65 and p50 nuclear translocation. It is also involved in BF-kB acetylation. BRMS1 suppressed OPN at the RNA and protein level. It interacts with HDAC3, which deacetylates p65. This causes NF-kB inactivation, which reduces OPN expression. Reduction of OPN expression by BRMS1 is either due to decrease in p65 trans-activation or reduction in NF-kB binding to the OPN