Insulin-like growth factor 1 stimulation of androgen receptor activity requires β1A integrins

✍ Scribed by Aejaz Sayeed; Naved Alam; Marco Trerotola; Lucia R. Languino

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 362 KB
• Volume: 227
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.22784

✦ Synopsis

Despite the findings that b1 integrins play a vital role in the regulation of cell proliferation and survival, the mechanisms through which they operate and lead to cancer progression remain elusive. Previously, our laboratory has shown that b 1A integrins support insulin-like growth factor 1 (IGFI)-mediated mitogenic and transforming activities. Here, we report that b 1A integrins regulate basal levels of IGF-IR, although they are not critical for maintaining cancer cell morphology. Upon transfection of b 1A siRNA and consequent downregulation of IGF-IR, we show inhibition of anchorage-independent growth of prostate cancer cells, a function which is dependent on IGF-IR expression. In addition, we demonstrate that IGFI-mediated activation of androgen receptor (AR), known to occur in prostate cancer cells, requires expression of b 1A integrins as evaluated by luciferase reporter assays and immunoblotting analysis. Since b 1A integrin levels are increased by R1881 or dihydrotestosterone (DHT), our results imply that b 1A integrins support an androgen-enhanced feedback loop that regulates the expression of IGF-IR. b 1A integrins also regulate inducible levels of IGF-IR in cells stimulated by androgen or by a combination of androgen and IGFI, as evaluated by flow cytometric analysis and immunoblotting. Furthermore, upon transfection of b 1A siRNA and consequent downregulation of IGF-IR, neither activation of AKT, an effector of IGF-IR, nor AR levels are affected. We conclude that b 1A integrin expression is critical for maintaining the regulatory crosstalk between IGF-IR and AR.