title: Relationship between B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) and homologous recombination regulatory genes in invasive ductal breast carcinomas.
abstract: B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) is a Polycomb group protein that is able to induce telomerase activity, enabling the immortalization of epithelial cells. Immortalized cells are more susceptible to double-strand breaks (DSB), which are subsequently repaired by homologous recombination (HR). BRCA1 is among the HR regulatory genes involved in the response to DNA damage associated with the RAD51 protein, which accumulates in DNA damage foci after signaling H2AX, another important marker of DNA damage. Topoisomerase IIIß (topoIIIß) removes HR intermediates before chromosomal segregation, preventing damage to cellular DNA structure. In breast carcinomas positive for BMI-1 the role of proteins involved in HR remains to be investigated. The aim of this study was to evaluate the association between BMI-1 and homologous recombination proteins. Using tissue microarrays containing 239 cases of primary breast tumors, the expression of Bmi-1, BRCA-1, H2AX, Rad51, p53, Ki-67, topoIIIß, estrogen receptors (ER), progesterone receptors (PR), and HER-2 was analyzed by immunohistochemistry. We observed high Bmi-1 expression in 66 cases (27.6%). Immunohistochemical overexpression of BMI-1 was related to ER (p=0.004), PR (p<0.001), Ki-67 (p<0.001), p53 (p=0.003), BRCA-1 (p= 0.003), H2AX (p=0.024) and topoIIIß (p<0,001). Our results show a relationship between the expression of BMI-1 and HR regulatory genes, suggesting that Bmi-1 overexpression might be an important event in HR regulation. However, further studies are necessary to understand the mechanisms in which Bmi-1 could regulate HR pathways in invasive ductal breast carcinomas.
authors.affiliation: Department of Pathology, Riberão Preto Medical School, University of São Paulo, Riberão Preto, São Paulo, Brazil.
authors.forename: Giórgia Gobbi
authors.initials: GG
authors.lastname: da Silveira
authors.forename: João Paulo
authors.initials: JP
authors.lastname: Oliveira-Costa
authors.forename: Danilo Figueiredo
authors.initials: DF
authors.lastname: Soave
authors.forename: Juliana Silva
authors.initials: JS
authors.lastname: Zanetti
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ribeiro-Silva
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008875:Middle Aged; D008979:Moloney murine leukemia virus / Q000472:pathogenicity; D063150:Polycomb Repressive Complex 1 / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D059767:Recombinational DNA Repair / Q000235:genetics; D016662:Virus Integration / Q000235:genetics
chemical_list: C489421:Bmi1 protein, mouse; D011518:Proto-Oncogene Proteins; D063150:Polycomb Repressive Complex 1