A Novel Role for Integrin Linked Kinase in Breast Cancer
Final rept. 1 Sep 2000-31 Aug 2004
CLEVELAND CLINIC FOUNDATION OH
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Allelic loss at the short arm of chromosome 11 is one of the most common and potent events in the progression and metastasis of breast cancer. Here, we present evidence that the Integrin-Linked Kinase ILK gene maps to the commonly deleted chromosome 11p15.5 and suppresses malignant growth of human breast cancer cells both in vitro and in vivo. ILK is expressed iii normal breast tissue but not in metastatic breast cancer cell lines or in advanced breast cancers. Transtection of wild-type ILK into the MDA-MB-435 mammary carcinoma cells potently suppressed their growth and invasiveness in vitro, and reduced the cells ability to induce tumors and metastasize in athymic mice. Conversely, expression of the ankyrin repeat or catalytic domain mutants of ILK failed to suppress the growth of these cells. Growth suppression by ILK is not due to apoptosis but is mediated by its ability to block cell cycle progression in the Gl phase. These findings directly demonstrate that ILK deficiency facilitates neoplastic growth and suggest a novel role for the ILK gene in tumor suppression.
- Medicine and Medical Research