Co-localization of mutant p53 and amyloid-like protein aggregates in breast tumors.
P53 is one of the most important tumor suppressor proteins in human cancers. Mutations in the TP53 gene are common features of malignant tumors and normally correlate to a more aggressive disease. In breast cancer, these gene alterations are present in approximately 20% of cases and are characteristically of missense type. In the present work we describe TP53 mutations in breast cancer biopsies and investigate whether wild and mutant p53 participate in protein aggregates formation in these breast cancer cases. We analyzed 88 biopsies from patients residing in the metropolitan area of Rio de Janeiro, and performed TP53 mutation screening using direct sequencing of exons 5-10. Seventeen mutations were detected, 12 of them were of missense type, 2 nonsenses, 2 deletions and 1 insertion. The presence of TP53 mutation was highly statistically associated to tumor aggressiveness of IDC cases, indicated here by Elston Grade III (p<0.0001). Paraffin embedded breast cancer tissues were analyzed for the presence of p53 aggregates through immunofluorescence co-localization assay, using anti-aggregate primary antibody A11, and anti-p53. Our results show that mutant p53 co-localizes with amyloid-like protein aggregates, depending on mutation type, suggesting that mutant p53 may form aggregates in breast cancer cells, in vivo.
Departamento de Genética, Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alcantara Gomes, Rio de Janeiro 20550-013, Brazil.
Claudia B
CB
Levy
Ana C
AC
Stumbo
Ana P D
AP
Ano Bom
Elisabeth A
EA
Portari
Yraima
Y
Cordeiro
Yraima
Y
Carneiro
Jerson L
JL
Silva
Claudia V
CV
De Moura-Gallo
D000328:Adult; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000648:ultrastructure; D004273:DNA, Neoplasm / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D056726:Genetic Association Studies; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure
D000682:Amyloid; D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53