Invasive prostate carcinoma driven by c-Src and androgen receptor synergy.

Journal Article (Journal Article)

Cellular Src (c-Src) integrates a large number of signal transduction pathways regulating cell division, migration, and other aspects of cell physiology. Mutations of Src kinase have not been described in human prostate cancer, but evidence for increased levels of expression accompanying cancer progression has been reported. We analyzed overexpression of c-Src in naïve mouse prostate epithelium and observed no change in tubule formation frequency or histologic structure. However, when enhanced c-Src expression is coupled with enhanced expression of androgen receptor (AR), it results in a strong activation of Src kinase activity accompanied by activation of the MAPK pathway, and enhanced AR activity. Similar to the pathology induced by constitutively active c-Src(Y529F), the tubules progress to frank carcinoma with invasion and display markers of epithelial-to-mesenchymal transition. These combined results suggest that nonmutated Src kinase may play a more important role in the genesis and progression of prostate cancer than previously appreciated and that epigenetic changes that enhance the level of AR may select for enhanced expression of c-Src with accompanying activation and a strong drive to malignant progression.

Full Text

Duke Authors

Cited Authors

  • Cai, H; Babic, I; Wei, X; Huang, J; Witte, ON

Published Date

  • February 1, 2011

Published In

Volume / Issue

  • 71 / 3

Start / End Page

  • 862 - 872

PubMed ID

  • 21135112

Pubmed Central ID

  • PMC3032821

Electronic International Standard Serial Number (EISSN)

  • 1538-7445

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-10-1605

Language

  • eng

Conference Location

  • United States