title: Overexpression of p53 protein is a marker of poor prognosis in Mexican women with breast cancer.
abstract: Breast cancer (BC) is a disease with different clinical, histological and molecular characteristics, frequently presenting mutated tumour-suppressing genes and oncogenes. P53 is a known tumour suppressor that is often mutated in BC; several mutations in p53 inhibit its role as a transcriptional repressor of several oncogenes. Topoisomerase 2α (TOP2α) is a gene target of p53, and it is also a known target for anthracyclines. The aim of the present study, was to analyse the genetic alterations of p53 and TOP2α genes and their levels of protein expression, as well as their association with survival in Mexican women with BC. A total of 102 biopsies were collected (tumour and adjacent tissues) from patients with BC. To identify point mutations and deletions in the p53 gene, the Sanger sequencing method was carried out. Deletions or amplifications for TOP2α gene were determined using quantitative polymerase chain reaction (qPCR). In addition, the expression of the TOP2α and p53 proteins was evaluated by western blotting. Furthermore, p53 protein expression was analysed by proximity ligation assay (PLA)-qPCR. Only 28.5% of the patients were found to have triple-negative breast cancer (TNBC); the average age at the time of diagnosis of these patients was 50 years, and Scarff-Bloom-Richardson (SBR) histological grade III (p=0.0089). No differences in point mutations or deletions in p53, and deletions or amplifications as well as protein expression level of TOP2α were observed between patients with TNBC and non-TNBC patients. However, patients with TNBC showed p53 protein overexpression as determined by PLA-qPCR and western blotting (p<0.0001). Furthermore, we found an association between TOP2α amplification and overexpression of its protein in patients with TNBC (p<0.0001). Concerning p53, overexpression resulted in a lower survival in patients with BC.
authors.affiliation: National Institute of Genomic Medicine, México City, México.
authors.forename: Jisela
authors.initials: J
authors.lastname: Dimas-González
authors.affiliation: National Institute of Genomic Medicine, México City, México.
authors.forename: Vilma
authors.initials: V
authors.lastname: Maldonado-Lagunas
authors.affiliation: National Cancer Institute, México City, México.
authors.forename: José
authors.initials: J
authors.lastname: Díaz-Chávez
authors.affiliation: National Institute for Forestry, Agriculture and Livestock Research, Jiutepec, Morelos, México.
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: López-Arellano
authors.affiliation: State Cancer Institute 'Dr. Arturo Beltrán Ortega', Acapulco, Guerrero, México.
authors.forename: José
authors.initials: J
authors.lastname: Muñoz-Camacho
authors.affiliation: State Cancer Institute 'Dr. Arturo Beltrán Ortega', Acapulco, Guerrero, México.
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Terán-Porcayo
authors.affiliation: National Institute of Public Health, Cuernavaca, Morelos, México.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Lagunas-Martínez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008800:Mexico; D008875:Middle Aged; D011379:Prognosis; D017422:Sequence Analysis, DNA / Q000379:methods*; D016019:Survival Analysis; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004250:DNA Topoisomerases, Type II