In:
Journal of Cellular Physiology, Wiley, Vol. 227, No. 2 ( 2012-02), p. 751-758
Abstract:
Despite the findings that β1 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 β 1A integrins support insulin‐like growth factor 1 (IGFI)‐mediated mitogenic and transforming activities. Here, we report that β 1A integrins regulate basal levels of IGF‐IR, although they are not critical for maintaining cancer cell morphology. Upon transfection of β 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 β 1A integrins as evaluated by luciferase reporter assays and immunoblotting analysis. Since β 1A integrin levels are increased by R1881 or dihydrotestosterone (DHT), our results imply that β 1A integrins support an androgen‐enhanced feedback loop that regulates the expression of IGF‐IR. β 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 β 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 β 1A integrin expression is critical for maintaining the regulatory crosstalk between IGF‐IR and AR. J. Cell. Physiol. 227: 751–758, 2012. © 2011 Wiley Periodicals, Inc.
Type of Medium:
Online Resource
ISSN:
0021-9541
,
1097-4652
Language:
English
Publisher:
Wiley
Publication Date:
2012
detail.hit.zdb_id:
1478143-8
SSG:
12
