Retinoic acid receptors as regulators of human epidermal keratinocyte differentiation.

To examine the role of nuclear retinoic acid (RA) receptors (RARs) in the regulation of squamous differentiation in normal human epidermal keratinocytes (NHEK), we analyzed binding activity, mRNA expression, and transcriptional activity of the endogenously expressed RARs. Specific RA-binding activity eluted from size-exclusion HPLC with an apparent mol wt of 50 kilodaltons and was predominantly (greater than 95%) associated with the NHEK nuclear cell fraction. This RAR-binding activity represented in part the expression of RAR alpha and RAR gamma genes, whose transcripts were expressed in similar abundance in undifferentiated NHEK. Differentiation resulted in lower mRNA expression of RAR alpha relative to the mRNA expression of RAR gamma. Treatment of NHEK cells with 10(-6) M RA did not induce expression of RAR beta mRNA. Similarly, three squamous cell carcinoma cell lines derived from human skin and oral cavity expressed RAR alpha and RAR gamma transcripts, but not RAR beta transcripts. Transfection of N...