Targeting Mouse Double Minute 2 Homolog (MDM2) Oncogene in Breast Adenocarcinoma.

INTRODUCTION

Breast adenocarcinoma (BAC) is a leading cause of cancer-dependent morbidity and mortality in females worldwide. Concerning critical genes that are implicated in its onset and progression in BAC, the tumor suppressor protein Tp53 (gene locus: 17p13.1) and its negative regulator the Mouse Double Minute 2 Homolog (MDM2) - an oncogene (gene locus: 12q14.3) - form a significant feedback loop.

OBJECTIVE

The aim of the current molecular review was to investigate the MDM2 oncogene deregulation mechanisms in BAC and the corresponding targeted therapeutic approaches.

MATERIAL AND METHOD: A set of fifty (n=50) published papers in the international database of PubMed was selected based on the new exposed knowledge in the field of mdm2 gene and protein normal function and deregulation. They also focused on the anti-mdm2 targeted regimens in BAC. The following keywords were used: breast, cancer, oncogene, mdm2, targeted therapies.

RESULTS

Mdm2 oncogene amplification - combined or not with specific gene polymorphisms - is a crucial molecular event in BAC onset and progression. These genetic alterations negatively affect the Tp53-MDM2 balance and cell homeostasis in breast epithelia.

CONCLUSIONS

MDM2 oncogene overexpression - due predominantly to amplification - is a relatively frequent event in BAC. Understanding the impact of mdm2 on genetic substrate and biological behavior of BAC, many study groups have experimentally explored the role of specific anti-mdm2 agents and suggested a fragment of them for targeting its oncogenic activity in BACs characterized by specific genetic signatures.