Analysis of the transcriptional activity of the two most common p53 mutants found in human breast tumors that are associated with resistance to doxorubicin reveals that these mutations completely eliminate the ability of p53 protein to transactivate CD95 gene expression.
Based on in vivo studies, the growth of breast tumor and expression of CD31, Bcl-2 and nonfunctional p53 were inhibited more effectively by ES-R than by ES-Zn.
Because most ER-negative breast tumors express mutant p53, our results provide the foundation for future development of p38 inhibitors to target p38 for the treatment of p53 mutant and ER-negative breast cancers.
By an in silico approach we identified miR-30a as a putative p53 target and observed that in breast tumors reduced miR-30a expression correlated with p53 inactivation, lymph node positivity and poor prognosis.
CGH analysis of breast tumours in conjunction with telomerase status has supported early results suggesting the involvement of the telomerase hTR, c-myc and p53 genes in the control of telomerase activity.
CHEK2 mutations affecting kinase activity together with mutations in TP53 indicate a functional pathway associated with resistance to epirubicin in primary breast cancer.
Consistent with this hypothesis, several independent studies using different methodologies have found that breast tumors with altered p53 have a worse prognosis and are also more likely to have other poor prognostic factors.
Data from this population-based cohort confirmed that breast tumors in AA women most likely are more aggressive compared with breast tumors in W women and offer new evidence for possible racial/ethnic differences with regard to p53 alterations.
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.