RETINOIC ACID RECEPTOR AND RETINOID-X RECEPTOR EXPRESSION IN RETINOICACID-RESISTANT HUMAN TUMOR-CELL LINES

Retinoic acid (RA) has profound effects on cell proliferation and diff erentiation both in vitro and in vivo. Many human cell lines are known to be sensitive to the growth-inhibitory action of RA. We analyzed es tablished human solid tumor-derived cell lines for their RA sensitivit y. Growth inhibition by RA in monolayer was examined by [H-3]thymidine incorporation and cell proliferation. Here we report that 11 widely u sed human cell lines were RA resistant. The majority are carcinoma der ived (A-431, BT-20, C-41, ACHN, HCT116, 293, A549, and PA-1); two are sarcoma derived (Saos-2 and A673); and one is a melanoma cell line (A- 375). Since nuclear retinoid receptors are implicated in the biologica l effects of RA, we examined the expression of retinoic acid receptors (RARs) RARalpha, RARbeta, RARgamma, and the retinoid X receptors (RXR s) RXRalpha, RXRbeta, and RXRgamma in the RA-resistant cell lines by n orthern blotting and by RNase protection analysis for RARbeta. RARalph a transcripts were constitutively expressed in all cell lines. By cont rast, RARbeta was expressed in only seven RA-resistant cell lines (Sao s-2, ACHN, 293, A549, A-375, A673, and PA-1), and its level was enhanc ed by RA in some cases. In most cell lines, RARgamma expression was lo w and was not affected by RA. The RXR genes showed a very distinct exp ression pattern in the group of selected cell lines. In general, RXRal pha was the most abundantly expressed subtype, RXRbeta was expressed a t low levels, and RXRgamma could not be detected. In none of the RA-re sistant cell lines was RXR expression modulated by RA. The results pre sented here indicate that the resistance of these human tumor cell lin es to RA cannot be simply correlated with expression of RAR or RXR or both. (C) 1993 Wiley-Liss, Inc.