Cysteine-rich protein 61 (Cyr61) is a member of a family of growth 
factor-inducible immediate-early genes. It regulates cell adhesion, migration, 
proliferation, and differentiation and is involved in tumor growth. In our 
experiments, the role of Cyr61 in non-small cell lung cancer (NSCLC) was 
examined. Expression of Cyr61 mRNA was decreased markedly in four of five human 
lung tumor samples compared with their normal matched lung samples. NSCLC cell 
lines NCI-H520 and H460, which have no endogenous Cyr61, formed 60-90% fewer 
colonies after being transfected with a Cyr61 cDNA expression vector than cells 
transfected with the same amount of empty vector. After stable transfection of a 
Cyr61 cDNA expression vector, proliferation of both H520-Cyr61 and H460-Cyr61 
sublines decreased remarkably compared with the cells stably transfected with 
empty vector. The addition of antibody against Cyr61 partially rescued the 
growth suppression of both H520-Cyr61 and H460-Cyr61 cells. Cell cycle analysis 
revealed that both H520-Cyr61 and H460-Cyr61 cells developed G(1) arrest, 
prominently up-regulated expression of p53 and p21(WAF1), and had decreased 
activity of cyclin-dependent kinase 2. The increase of pocket protein pRB2/p130 
was also detected in these cells. Notably, both of the Cyr61-stably transfected 
lung cancer cell lines developed smaller tumors than those formed by the 
wild-type cells in nude mice. Taken together, we conclude that Cyr61 may play a 
role as a tumor suppressor in NSCLC.