Genes encoding proteins that have key functions in the DNA damage response, such as p53 and its inhibitors MDM2 and MDMX, are most likely candidates to harbor allelic variants that influence breast cancer susceptibility.
MDM2 drives TNBC circulating tumor cells (CTCs) in mice, but the context-dependent influences of MDM2 and MDMX on different subtypes of breast cancers expressing mtp53 have not been determined.
Altogether, these findings suggest that SCF<sup>FBXO22</sup> targets HDM2 for degradation and possesses inhibitory effects against breast cancer tumor cell invasion and metastasis.
In conclusion, oncoprotein HBXIP suppresses miR-18b to elevate MDM2 and activates pAKT to phosphorylate MDM2 for enhancing the interaction between MDM2 and p53, leading to p53 degradation in promotion of breast cancer growth.
Together, our finding revealed a novel modifier for p53/MDM2 complex and suggested SHARPIN as a promising target to restore p53 function in breast cancer.
Allele 399Gln (OR 1.57; 95% CI 1.05-2.35), Arg399Gln of gene XRCC1 heterozygous genotype (OR 2.77; 95% CI 1.60-4.80), the combination of Arg399Gln/Arg72Pro of genes XRCC1/TP53 heterozygous genotype (OR 3.98; 95% CI 1.57-10.09), Arg399Gln/T309G of genes XRCC1/MDM2 (OR 3.0; 95% CI 1.18-7.56), as well as Arg399Gln/Arg72Pro/T309G of genes XRCC1/TP53/MDM2 (OR 6.40; 95% CI 1.18-34.63) were associated with BC in Kyrgyz women.
Taken together these data indicate that in some ER+ breast cancers the estrogen-MDM2-Rb-E2F1 axis is a central hub for estrogen-mediated p53-independent signal transduction.
We also propose several strategies for inhibiting the NFAT1-MDM2-p53 pathway, which could be useful for developing more specific and effective inhibitors for breast cancer therapy.
We report that the expression of MDM4 and MDM2 is elevated in primary human breast cancers of luminal A/B subtypes and associates with ERα-positive disease, independently of p53 mutation status.
In summary, we report for the first time that SQ shows excellent anti-breast cancer activity in vivo and in vitro and induces p53-independent apoptosis, which is associated with MDM2 inhibition.
In this study, we investigated the role of MDM2 in epithelial-to-mesenchymal transition (EMT) and the underlying mechanisms in breast cancer cells in vitro and in vivo.
Platycodin D, a metabolite of Platycodin grandiflorum, inhibits highly metastatic MDA-MB-231 breast cancer growth in vitro and in vivo by targeting the MDM2 oncogene.
In conclusion, G613 represents a potent small-molecule inhibitor of the Mdm2-p53 interaction and can serve as a promising lead for developing a new class of anti-cancer therapy for breast cancer patients.
However, the results obtained from the combination of SNPs 344T>A of MDM2 and 72 Arg/Pro of p53, do not support the hypothesis of the prominent role of common p53 and MDM2 variations in the genetic mechanisms of chemotherapy resistance in breast cancer.