Suppression of malignant growth of human breast cancer cells by ectopic expression of integrin-linked kinase.
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 in normal breast tissue but is downregulated in metastatic breast cancer cell lines and in advanced breast cancers. Transfection 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 nude 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 G1 phase and by modulating the levels of integrins. These findings directly demonstrate that ILK deficiency facilitates neoplastic growth and invasion and suggest a novel role for the ILK gene in the suppression of tumor metastasis.
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Ping
P
Chen
Wei-Zhen
WZ
Shen
Pratima
P
Karnik
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D002453:Cell Cycle; D002455:Cell Division; D002465:Cell Movement; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology*; D000099200:Scaffold Protein ILK
D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK