The molecular biology of lung cancer pathogenesis.

Abstract

Lung cancers exhibit multiple genetic lesions including mutations activating the dominant cellular proto-oncogenes as well as those inactivating the recessive or "tumor suppressor" genes. Candidate tumor suppressor genes include those on chromosomes 1p, 1q, 3p14, 3p21.3, 3p25 (VHL gene), 5q21 (APC/MCC gene cluster), 9p21-22 (interferon gene cluster), 11p, 13q (rb gene), 16p24, and 17p (p53 gene). Mutations in p53 inactivate its transcriptional activity, while replacement of a wild-type p53 in lung cancer cells inhibits growth and tumorigenicity suggesting that p53 acts as a master growth regulatory switch. Lung cancer cells exhibit several positive autocrine growth factor loops and express nicotine receptors which could function as tumor promoting systems. In addition, they express a negative autocrine loop involving opioids and their receptors which is reversed by nicotine acting through nicotinic acetylcholine receptors. The presence of nicotine receptors suggests nicotine or its metabolites may play a direct role in lung cancer pathogenesis.