Abstract

Oncogenic transformation of growth factors, growth factor receptors, transcription factors as well as important cellular proteins and their association with the principal tumor suppressor p53 may provide essential insights toward integrated therapy in breast cancer. In this review we discuss growth factor HER-2/neu receptor tyrosine kinase; FAK, non-receptor tyrosine kinase; TGF-β, and their roles in tumorigenesis in breast cell with respect to p53. VEGF is a powerful angiogenic factor and its expression is also regulated by p53. E3 ligases like MDM2 and cullin 7 are considered as oncoproteins and they interact differently with p53 in breast cells. Aberrant expression of these ligases is associated with tumorigenesis. The transcription factor cyclin E is involved in cell cycle progression while its activity is subjected to p53 regulation through p21. The necrosis factor NF-κB regulates p53 expression by binding to its promoter and modulates expression of anti-apoptotic protein survivin in breast cancer cell. Apoptosis by Bcl-2 family of protein is largely dependent upon the balance of pro-apoptotic and anti-apoptotic protein expression regulated by p53. In essence, the complexities of p53 interactions with various types of oncogene products require close exploration towards an integrated therapy against breast cancer.

Keywords: Anti-sense oligonucleotide, Bcl-2, breast cancer, epithelial to messenchymal transition (EMT), FAK, HER-2/neu, MDM2 and cullin 7, NF-κB, oncogene, p21, p53, reactive oxygen species (ROS), siRNA, survivin, TGF-β, tumor suppressor, VEGF.

Graphical Abstract