LUNG-CANCER, RETINOIDS AND RETINOIC ACID RECEPTOR-BETA

Lung cancer comprises a group of histologically distinct malignancies - small cell, epidermoid, adenocarcinoma and large cell - which are co llectively responsible for the largest number of cancer-related deaths in Western societies. The molecular changes associated with this dise ase am both genetically dominant (activation of oncogenes) and recessi ve (mutation and/or silencing of tumour suppressor genes). Among the l atter, deletions on the short arm of chromosome 3 are thought to play a major role, since they are frequently seen in lung cancer. The beta receptor of retinoic acid (RARbeta) in chromosome band 3p24 is an inte resting candidate suppressor gene, especially for epidermoid lung canc er. Cells derived from these cancers, which do not express RARbeta, ha ve been transfected with the cDNA of this gene, and substantial reduct ion in tumorigenicity is noted. The few tumours which do appear genera lly express much lower. levels of RARbeta than the corresponding trans fected cells in culture. Thus loss of RARbeta expression appears to be a step in tumorigenesis. A recent provocative report that one of the first events occurring tn precancerous lung lesions is loss of one cop y of the short arm of chromosome 3 suggests even partial reduction in RARbeta protein levels, may trigger the neoplastic process. These resu lts also offer an interesting molecular level explanation of how retin oic acid may be useful in prevention and treatment of lung cancer.