IMPLICATION OF RETINOIC ACID RECEPTOR-BETA IN RENAL-CELL CARCINOMA

The retinoic acid receptor (RAR) beta gene is located in a region on c hromosome 3p, which is frequently deleted in renal cell carcinoma. Sin ce retinoic acid (RA) can inhibit cell proliferation and tumor formati on, loss of RAR beta might contribute to oncogenesis of the kidney. Th is prompted us to examine RAR beta expression in 12 primary kidney tum ors and 11 renal cancer cell lines. Five tumors expressed RAR beta at severely reduced levels, three of which have retained one gene copy. I n one tumor an aberrant larger transcript was expressed. Only three ce ll lines showed detectable expression of RAR beta, albeit at low level s in comparison with normal kidney cells, and in most cases RA could n ot inhibit cell proliferation. To investigate the involvement of RARB in RA-dependent growth control, we stably transfected RAR beta express ion vectors into two of the renal cancer cell lines. RAR beta-expressi ng clones' derived from SK-RC-35 showed a markedly reduced proliferati on in the presence of RA, whereas the growth of parental cells was not affected. Transfectants derived from SK-RC-48, also showed inhibition of growth when exposed to RA. However, these transfectants responded only to high doses of RA. Taken together, our data support the possibi lity that RAR beta is implicated in the development of renal cell carc inomas.