Cancer du poumon, rétinoïdes et récepteur β de l'acide rétinoïque

Abstract

Lung cancer comprises a group of histologically distinct malignancies - small cell, epidermoid, adenocarcinoma and large cell - which are collectively responsible for the largest number of cancer-related deaths in Western societies. The molecular changes associated with this disease am both genetically dominant (activation of oncogenes) and recessive (mutation and/or silencing of tumour suppressor genes). Among the latter, 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 interesting candidate suppressor gene, especially for epidermoid lung cancer. Cells derived from these cancers, which do not express RARbeta, have been transfected with the cDNA of this gene, and substantial reduction in tumorigenicity is noted. The few tumours which do appear generally express much lower. levels of RARbeta than the corresponding transfected 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 copy of the short arm of chromosome 3 suggests even partial reduction in RARbeta protein levels, may trigger the neoplastic process. These results also offer an interesting molecular level explanation of how retinoic acid may be useful in prevention and treatment of lung cancer.