ERα Mediates Estrogen-Induced Expression of the Breast Cancer Metastasis Suppressor Gene BRMS1

ABSTRACT The antiapoptotic transcription factor NF-κB is constitutively activated in many cancers and is important for cytokine-mediated progression and metastatic movement of tumors. Breast cancer metastasis suppressor 1 (BRMS1) is a metastasis suppressor gene whose mechanisms of action are poorly understood. In this report, we demonstrate that BRMS1 decreases the transactivation potential of RelA/p65 and ameliorates the expression of NF-κB-regulated antiapoptotic gene products. BRMS1 immunoprecipitates with the RelA/p65 subunit of NF-κB with protein-protein interactions occurring at the C terminus region of the rel homology domain but not at its known transactivation domains. Moreover, BRMS1 functions as a corepressor by promoting binding of HDAC1 to RelA/p65, where it deacetylates lysine K310 on RelA/p65, which suppresses RelA/p65 transcriptional activity. Selective small interfering RNA knockdown of BRMS1 confirms that chromatin-bound BRMS1 is required for deacetylation of RelA/p65, while enhancing chromatin occupancy of HDAC1 onto the NF-κB-regulated promoters cIAP2 and Bfl-1/A1. We observed in cells lacking BRMS1 a dramatic increase in cell viability after the loss of attachment from the extracellular matrix. Collectively, these results suggest that BRMS1 suppresses metastasis through its ability to function as a transcriptional corepressor of antiapoptotic genes regulated by NF-κB.

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Polymorphisms rs12998 and rs5780218 inKiSS1Suppressor Metastasis Gene in Mexican Patients with Breast Cancer

Disease Markers ◽

10.1155/2015/365845 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Edhit Guadalupe Cruz Quevedo ◽

Gabriela Monserrat Mimendi Aguilar ◽

Luis Anselmo Juárez Aguilar ◽

Susan Andrea Gutierrez Rubio ◽

Silvia Esperanza Flores Martínez ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Metastasis ◽

Benign Breast Disease ◽

Breast Disease ◽

Suppressor Gene ◽

Breast Cancer Metastasis ◽

Breast Cancer Cell Lines ◽

Metastasis Suppressor ◽

Metastasis Suppressor Gene ◽

Cancer Studies

Aims. KiSS1is a metastasis suppressor gene associated with inhibition of cellular chemotaxis and invasion attenuating the metastasis in melanoma and breast cancer cell lines. Along theKiSS-1gene at least 294 SNPs have been described; however the association of these polymorphisms as genetic markers for metastasis in breast cancer studies has not been investigated. Here we describe two simple PCR-RFLPs protocols to identify the rs5780218 (9DelT) and the rs12998 (E20K)KiSS1polymorphisms and the allelic, genotypic, and haplotypic frequencies in Mexican general population (GP) and patients with benign breast disease (BBD) or breast cancer (BC).Results.The rs5780218 polymorphism was individually associated with breast cancer(P=0.0332)and the rs12998 polymorphism shows statistically significant differences when GP versus case (BC and BBD) groups were compared(P<0.0001). The H1 Haplotype (G/-) occurred more frequently in BC group (0.4256) whereas H2 haplotype (G/T) was the most prevalent in BBD group (0.4674).Conclusions.Our data indicated that the rs5780218 polymorphism individually confers susceptibility for development of breast cancer in Mexican population and a possible role as a genetic marker in breast cancer metastasis for H1 haplotype (Wt/variant) inKiSS1gene must be analyzed in other populations.

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