Retinoic acid receptor beta (
RAR beta), which codes for a
nuclear receptor for
retinoic acid, is localized in a chromosomal region frequently deleted in
lung cancer cells. The gene is expressed in normal lung tissue and in the majority of the cell lines derived from lung
tumors but not in most of the lines derived from lung
tumors with epidermoid characteristics. To study the possible role of
RAR beta in growth control of epidermoid lung
tumor-derived cells, transfectants expresing
RAR beta were generated from nonexpressing epidermoid
tumor-derived cell lines. Four clones were derived from line CALU-1, three of which showed a 20-60% increase in doubling time in the presence of
retinoic acid. Parental and control-transfected cells were unaffected or slightly stimulated. All four clones expressing
RAR beta were less tumorigenic in nude mice than were the untransfected or control-transfected cells, with about a 50% incidence of take vs. 95%. When
tumors did develop from
RAR beta-positive cells, they showed a reduced rate of growth, an increased latency, and, in six of seven
tumors tested, a much reduced level of
RAR beta expression. Transfectants derived from a second
tumor line, H157, also showed a markedly reduced incidence of take in nude mice. Together with the known effects of
retinoic acid on differentiation and
carcinogenesis, our results support the hypothesis that
RAR beta functions as a tumor suppressor gene in epidermoid lung
tumorigenesis.