The retinoic acid receptor (RAR) beta gene is located in a region on chromosome 3p, which is frequently deleted in renal cell carcinoma. Since retinoic acid (RA) can inhibit cell proliferation and tumor formation, loss of RAR beta might contribute to oncogenesis of the kidney. This prompted us to examine RAR beta expression in 12 primary kidney tumors and 11 renal cancer cell lines. Five tumors expressed RAR beta at severely reduced levels, three of which have retained one gene copy. In one tumor an aberrant larger transcript was expressed. Only three cell lines showed detectable expression of RAR beta, albeit at low levels in comparison with normal kidney cells, and in most cases RA could not inhibit cell proliferation. To investigate the involvement of RARB in RA-dependent growth control, we stably transfected RAR beta expression vectors into two of the renal cancer cell lines. RAR beta-expressing clones' derived from SK-RC-35 showed a markedly reduced proliferation 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 possibility that RAR beta is implicated in the development of renal cell carcinomas.

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