Protective function of p27(KIP1) against apoptosis in small cell lung cancer cells in unfavorable microenvironments

A previous study of ours unexpectedly found that in contrast to frequent re ductions in non-small cell lung cancer, high expression of the p27(KIP1) cy clin-dependent kinase (CDK) inhibitor was retained in virtually all small c ell lung cancers (SCLCs), suggesting the possibility of high expression of nonfunctional p27(KIP1) in this virulent tumor. The study presented here, h owever, shows that p27(KIP1) in SCLC biochemically functions as a CDK inhib itor, clearly showing induction apparently associated with G(1)/G(0) arrest and efficient binding to and inhibition of the cyclin E-CDK2 complex. Inte restingly, induction of p27(KIP1) seems to confer on SCLC cells the ability to survive under culture conditions unfavorable for cell growth such as a lack of nutrients and hypoxia. Subsequent experiments manipulating p27(KIP1 ) levels by using a sense p27(KIP1) expression construct or an antisense ol igonucleotide supported this notion. These observations suggest that high e xpression of p27(KIP1) in vivo may favor the survival of SCLC by preventing apoptosis in a microenvironment unfavorable for cell proliferation.