We examined the association of clinical and pathological characteristics of breast tumors and breast cancer risk factors according to the prevalence and type of p53 mutations.
The association of lymphocytic invasion of ER-negative breast tumors with the retention of wild-type TP53 implies a novel protective connection between TP53 function and tumor immunosurveillance.
Through the described mechanism, elevated CXCR5 expression may contribute to abnormal cell survival and migration in breast tumors that lack functional p53.
These results have translational relevance, demonstrating that TP53 mutant breast tumor growth can be suppressed by pharmacologic TLR4 inhibition, whereas TLR4 inhibitors may in fact promote growth of TP53 wild-type tumors.
We have predicted three deleterious coding non-synonymous single nucleotide polymorphisms rs11540654 (rs11540654" genes_norm="7157">R110P), rs17849781 (rs17849781" genes_norm="7157">P278A) and rs28934874 (rs28934874" genes_norm="7157">P151T) in TP53 with a phenotype in breast tumors using computational tools SIFT, Polyphen-2 and MutDB.
Furthermore, Notch-induced transcriptomes from p53 wild-type and -mutated breast tumor cell lines differed extensively, and for a subset of genes upregulated by Notch in a p53-mutant cell line, this upregulation was reduced by wild-type p53.
Through search for other possible p53 E3 ligases by mRNA and protein expression analysis, downregulation of TNF receptor-associated factor 7 (TRAF7) expression was found in these breast tumors.
In this study we assessed the effects of the phytocompounds garcinol and curcumin on histone and p53 modification in cancer cells, focussing on the breast tumour cell line MCF7.
Our results showed that telomeres were significantly shorter in tumors with somatic p53 mutations compared with tumors with wild-type p53 in both breast tumors (P=0.007) and esophageal cancer (P=0.001).
Deletion of TP53 was the most frequent alteration observed, suggesting that if this alteration is present in the primary tumors, breast tumors with loss of TP53 copies have a poorer prognosis and a higher chance for metastasis.
We have previously tested biopsies from 1469 breast tumours with a p53 functional assay in the context of a prospective clinical trial (EORTC 10994/BIG 1-00).
In this study, expression of mature miR-34a in breast tumors with wild-type p53 was investigated in order to find any correlation between dysregulation of miR-34a expression and breast cancer.
Expression of EXO1 module was found as indicative of elevated cell proliferation, genomic instability, activated RAS/AKT/MYC/E2F1 signaling pathways and loss of p53 activity in breast tumors. mRNA-drug connectivity analysis indicates inhibition of RAS/PI3K as a possible targeted therapeutic approach for the patients with activated EXO1 module in breast tumors.
Here we describe the analysis of BRCA1, PTEN, and p53 at the single cell level in 55 BRCA1-associated breast tumors and computational methods to predict the relative temporal order of somatic events, on the basis of the frequency of cells with single or combined alterations.
These results suggest that specific p53 mutations may contribute to loss of estrogen receptor α expression in breast tumors and also support the hypothesis that mutant p53 is likely to impact DNA methylation.
The Oncomine database was explored for TrxR1 (TXNRD1) expression in breast tumors and TrxR1, ER and p53 expression was analyzed by immunohistochemistry in a panel of breast tumors.