MYC in breast tumor progression

Abstract

Breast cancer is the second leading cause of cancer deaths and is the most frequently diagnosed cancer in women of industrialized nations. Breast cancer progression is a multistep process involving genetic and epigenetic alterations that drive normal breast cells into highly malignant derivatives with metastatic potential. MYC is a proto-oncogene whose protein product contains a basic helix–loop–helix domain. MYC functions as a transcription factor regulating up to 15% of all human genes. MYC is regulated at multiple levels, and the protein is a downstream effector of several signaling pathways. In breast cancer cells, MYC target genes are involved in cell growth, transformation, angiogenesis and cell-cycle control. BRCA1 is linked to transcriptional regulation through interaction with MYC. Although the relationship between amplification and overexpression is not clearly delineated, MYC amplification is significantly correlated with aggressive tumor phenotypes and poor clinical outcomes. MYC amplification is emerging as an important predictor of response to HER2-targeted therapies and its role in BRCA1-associated breast cancer makes it an important target in basal-like/triple-negative breast cancers.