We show that, in breast cancer-derived cell lines, the increase in rRNA transcription that follows JHDM1B knock-down is mirrored by an augmented cell proliferation only in p53 compromised cells, while p53 competent cells undergo cellular senescence and death.
Taken together, these biochemical and functional data are the first demonstration that (a) wild-type p53 protein binds to a response element within the EpCAM gene and negatively regulates EpCAM expression, and (b) transcriptional repression of EpCAM contributes to p53 control of breast cancer invasion.
We conclude from these studies that ER expression and P53 alteration may constitute early steps in progression of malignant potential for breast cancer development.
Sequential ablation of survivin phosphorylation on Thr(34) enhanced tumor cell apoptosis induced by anticancer agents independently of p53 and suppressed tumor growth without toxicity in a breast cancer xenograft model in vivo.
These findings suggest that breast cancer developing on a background of an inherited TP53 mutation is highly likely to present with amplification of HER2.
We therefore tested the hypothesis that taxanes confer a greater advantage than do anthracyclines on breast cancers with mutated TP53 than in those with wild-type TP53.
The aim of this case-control study conducted in Nagoya, Japan, was to reconfirm the results of prior studies of polymorphisms of p53Arg72Pro, and to test if polymorphisms of p73 G4C14-to-A4T14 at exon 2 (G4A) were also associated with breast cancer risk.
Mutation in TP53 occurs at high frequency in carcinomas of the lung and gastro-intestinal tract, but is much less frequent, at 25%, in primary breast cancer.
Although inherited breast cancer has been associated with germline mutations in genes that are functionally involved in the DNA homologous recombination repair (HRR) pathway, including BRCA1, BRCA2, TP53, ATM, BRIP1, CHEK2 and PALB2, about 70% of breast cancer heritability remains unexplained.
Our results suggest that TP53 c.215G>C, p. (Arg72Pro) polymorphism may be considered as a genetic marker for predisposition to BC in Moroccan population.
In addition, TP53 loss of heterozygosity (LOH), methylation, and mutations were studied in tumor DNA of BC individuals with loss of alleles of TP53 polymorphisms.
We intended to establish the frequency of exon-specific TP53 gene alterations and the relation to patient and tumor characteristics and clinical outcome of patients with breast cancer.