Β1 integrins mediate resistance to ionizing radiation in vivo by inhibiting c‐Jun amino terminal kinase 112. Issue 7 (21st March 2013)

• Record Type: Journal Article
• Authors: Goel, Hira Lal; Sayeed, Aejaz; Breen, Michael; Zarif, Matthew J.; Garlick, David S.; Leav, Irwin; Davis, Roger J.; FitzGerald, Thomas J.; Morrione, Andrea; Hsieh, Chung‐Cheng; Liu, Qin; Dicker, Adam P.; Altieri, Dario C.; Languino, Lucia R.
• Is Part Of: Journal of cellular physiology. Volume 228:Issue 7(2013:Jul.)
• Page Start: 1601
• Page End: 1609
• Publication Date: 2013-03-21
• Subjects: Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.24323
• Languages: English
• ISSNs: 0021-9541

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>This study was carried out to dissect the mechanism by which β<sub>1</sub> integrins promote resistance to radiation. For this purpose, we conditionally ablated β<sub>1</sub> integrins in the prostatic epithelium of transgenic adenocarcinoma of mouse prostate (TRAMP) mice. The ability of β<sub>1</sub> to promote resistance to radiation was also analyzed by using an inhibitory antibody to β<sub>1</sub>, AIIB2, in a xenograft model. The role of β<sub>1</sub> integrins and of a β<sub>1</sub> downstream target, c‐Jun amino‐terminal kinase 1 (JNK1), in regulating radiation‐induced apoptosis in vivo and in vitro was studied. We show that β<sub>1</sub> integrins promote prostate cancer (PrCa) progression and resistance to radiation in vivo. Mechanistically, β<sub>1</sub> integrins are shown here to suppress activation of JNK1 and, consequently apoptosis, in response to irradiation. Downregulation of JNK1 is necessary to preserve the effect of β<sub>1</sub> on resistance to radiation in vitro and in vivo. Finally, given the established crosstalk between β<sub>1</sub> integrins and type1 insulin‐like growth factor receptor (IGF‐IR), we analyzed the ability of IGF‐IR to modulate β<sub>1</sub> integrin levels. We report that IGF‐IR regulates the expression of β<sub>1</sub> integrins, which in turn confer resistance to radiation in PrCa cells. In conclusion, this study demonstrates that β<sub>1</sub> integrins mediate resistance to ionizing radiation through inhibition of JNK1 activation. J. Cell. Physiol. 228: 1601–1609, 2013. © 2013 Wiley Periodicals, Inc.</p> </abstract>