Chapter 8 The Roles and Action Mechanisms of p160/SRC Coactivators and the ANCCA Coregulator in Cancer

Chromosomal aberrations involving genes encoding members of the p160/SRC transcriptional coactivator family such as AIB1/ACTR and TIF2 implicated the coactivators in malignancy of human cells. Significant progress has been made in the last decade toward uncovering their roles in the development and progression of solid tissue tumors as well as leukemia and understanding of the underlying molecular mechanisms. Here, we review their genetic aberrations and dysregulation in expression in breast cancer, prostate cancer, and other nonhormone-responsive cancers. The experimental evidence gathered from studies using cell culture and animal models strongly supports a critical and, in some circumstances, their oncogenic function. We summarize results that the SRCs may contribute to tumorigenesis and disease progression through transcription factors such as E2F, PEA3, and AP-1 and through an intimate control of signaling pathways of growth factors-Akt and the receptor tyrosine kinases. The finding that a recently identified nuclear receptor coregulator ANCCA, like the SRCs, is frequently overexpressed in many types of cancers again underscores their broader roles in cancer.