1. ¹Cancer Research Program, Research Institute, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8
2. ²Department of Laboratory Medicine and Pathobiology, University of Toronto
3. ³Departments of Medicine and Genetics, Gastroenterology Division, Abramson Cancer Center, University of Pennsylvania, 600 CRB, 415 Curie Blvd., Philadelphia, PA 19104, USA

Correspondence: GE Hannigan, E-mail: hannigan@sickkids.ca

Received 10 March 2004; Revised 29 July 2004; Accepted 9 August 2004; Published online 4 October 2004.

Abstract

We analysed breast tumors and breast cancer cell lines for the expression of -parvin (ParvB), an adaptor protein that binds to the integrin-linked kinase (ILK). Quantitative RT–PCR indicated that ParvB mRNA was downregulated, by at least 60%, in four of nine breast tumors, relative to patient-matched normal mammary gland tissue. We also found that ParvB protein levels were reduced by 90% in five of seven advanced tumors, relative to matched normal breast tissue. Conversely, ILK protein and kinase activity levels were elevated in these tumors, suggesting that downregulation of ParvB stimulates ILK signaling. Western blot analyses indicated very low levels of ParvB protein in MDA-MB-231 and MCF7 breast cancer cells, facilitating functional studies of the effects of ParvB on ILK signaling. Expression of ParvB in MDA-MB-231 and MCF7 cells increased cell adhesion to collagen. ParvB inhibited ILK kinase activity, anchorage-independent cell growth and in vitro matrigel invasion by MDA-MB-231 cells. EGF-induced phosphorylation of two ILK targets, PKB (Ser473) and glycogen synthase kinase 3 (Ser9), was also inhibited by ParvB. These results indicated that ParvB inhibits ILK signaling downstream of receptor tyrosine kinases. Our results suggest that loss of ParvB expression is a novel mechanism for upregulating ILK activity in tumors.