Pulldown assays, used to search for proteins capable to selectively bind tRF3E, have shown that this tRF specifically interacts with nucleolin (NCL), an RNA-binding protein overexpressed in BC and able to repress the translation of p53 mRNA.
In this study we have analyzed mRNA expression of both wild-type and mutated p53 and its respective Deltap53 isoform in 88 tumor samples from breast cancer in relation to clinical parameters and molecular subgroups.
Immunohistochemical analysis demonstrated overexpression of the p53 gene product in 38 of 84 (45%) ovarian carcinomas, as against 10 of 42 (24%) breast carcinomas (P = 0.0195). p53 immunoreactivity was significantly associated with LOH in ovarian and breast cancers.
Germline alterations of the tumour suppressor TP53 gene are detected approximately in 25% of the families suggestive of Li-Fraumeni syndrome (LFS), characterised by a genetic predisposition to a wide tumour spectrum, including soft-tissue sarcomas, osteosarcomas, premenopausal breast cancers, brain tumours, adrenocortical tumours, plexus choroid tumours, leukaemia and lung cancer.
These results demonstrate that a loss of BRCA1 function results in the growth of breast cancers with CIN, and this phenotype is further accelerated by p53 abnormality.
The clonogenic growth of breast cancer cell lines was inhibited by a ligand for PPARgamma (troglitazone, TGZ) combined with a ligand for either retinoid X receptor (RXR) (LG10069) (4/8 cell lines), RAR (ATRA) (5/8 cell lines) or RAR/RXR and RXR/RXR (9-cis-RA) (5/8 cell lines) independent of their expression of bcl-2, bag-1, ERalpha, and p53.
We investigated whether histone deacetylase inhibitor trichostatin A (TSA), in combination with p53 gene transfer could synergistically induce apoptosis in the breast cancer cell line MDA-MB-231.
We conclude that, compared to amplification of HER2/NEU, MYC, or INT2 oncogene loci, p53 gene mutations and deletions are the most frequently observed genetic change in breast cancer related to a single gene.
BRCA1 and BRCA2 mutations confer very high risks of breast and ovarian cancer. p53 and PTEN mutations lead to very high breast cancer risks associated with rare cancer syndromes.
Since germ line mutations in the tumor suppressor gene TP53 predispose women to early-onset breast cancer, we assessed the prevalence of TP53 mutations in 105 early-onset breast cancer patients from Pakistan, who had previously been found to be negative for BRCA1 and BRCA2 germ line mutations.
The tumor cell line is marked by multiple additional genetic changes including a high degree of aneuploidy, an acquired mutation of TP53 with wild-type allele loss, an acquired homozygous deletion of the PTEN gene, and loss of heterozygosity at multiple loci known to be involved in the pathogenesis of breast cancer.
In conclusion, this study shows that TRIM22 is greatly under-expressed in breast cancer. p53 dysfunction may be one of the mechanisms for TRIM22 down-regulation.
Our results indicate that both BstUI and MspI p53 polymormphisms might play the role in the breast cancer development especially in women younger than 50 years.
These results have implications for the stratification of breast cancer based on p53 function and may provide an alternate explanation for deregulated p53 signalling in breast cancer.
The Prognostic Value of the Immunohistochemical Expression of Phosphorylated RB and p16 Proteins in Association with Cyclin D1 and the p53 Pathway in a Large Cohort of Patients with Breast Cancer Treated with Taxane-based Adjuvant Chemotherapy.
Samples for the analysis of DNA ploidy, estrogen receptor (ER), progesterone receptor (PgR), p53 protein and epidermal growth factor receptor (EGFR) were prepared from the same frozen specimens of 498 primary breast cancers.
Multivariate analysis of 153 patients for whom full data were available showed that p53 status contributed prognostic information when tumour size and lymph node status were taken into account but not when histological grade was included. p53 status thus contributes only limited new prognostic information in breast cancer when established prognostic factors are taken into account.Int.J.Cancer (Pred.Oncol.)84:587-593, 1999.
Using these statistics we demonstrate that 1) breast cancer cell fate after chemotherapy is dependent on p53 genotype; 2) granulocyte macrophage progenitors and their differentiated progeny have concordant fates; and 3) cytokines promote self-renewal of cardiac mesenchymal stem cells by symmetric divisions.
Annotation using TCGA (The Cancer Genome Atlas) database revealed that p53 negatively regulated mRNA expression of several cancer therapeutic targets or pathways such as BTK, SYK, and CTLA4 in breast cancer tissues.
Genes relatively hypermethylated in HR+, luminal A, or p53 wild-type breast cancers included FABP3, FGF2, FZD9, GAS7, HDAC9, HOXA11, MME, PAX6, POMC, PTGS2, RASSF1, RBP1, and SCGB3A1, whereas those more highly methylated in HR-, basal-like, or p53 mutant tumors included BCR, C4B, DAB2IP, MEST, RARA, SEPT5, TFF1, THY1, and SERPINA5.
We have examined the effects of a replication-defective adenovirus encoding p53 (RPR/INGN 201 [Ad5CMV-p53]; Adp53), alone or in combination with the breast cancer therapeutic doxorubicin (Adriamycin), to suppress growth and induce apoptosis in breast cancer cells in vitro.