MODULATION BY RETINOIC ACID (RA) OF SQUAMOUS-CELL DIFFERENTIATION, CELLULAR RA-BINDING PROTEINS, AND NUCLEAR RA RECEPTORS IN HUMAN HEAD ANDNECK SQUAMOUS-CELL CARCINOMA CELL-LINES

The ability of all-trans-retinoic acid (RA) to modulate the growth and squamous differentiation of four head and neck squamous cell carcinom a cell lines (183, 886, 1483, and SqCC/Y1) was examined, and the relat ionship of their state of squamous differentiation and RA responsivene ss to the expression of cytosolic RA-binding proteins (CRABPs), nuclea r RA receptors (RARs), and retinoid X receptors (RXRS) was investigate d. RA inhibited proliferation of all but the 183 cell line and suppres sed squamous differentiation markers K1 keratin, type 1 transglutamina se, and involucrin mRNAs and proteins to varying degrees in 183, 1483, and SqCC/Y1 cells. Traces of CRABP-I mRNA were detected only in the 8 86 cells, whereas CRABP-II mRNA was detected in the other three cell l ines. RA suppressed CRABP-II expression in SqCC/Y1 cells but had no ef fect on its expression in the other cell lines. All cell lines express ed mRNAs for RAR-alpha, RAR-beta, RAR-gamma, and RXR-alpha. The RAR-be ta mRNA level was lowest in the SqCC/Y1 cells, and RXR-beta and RXR-ga mma were not detected in any of the cell lines. RA treatment increased the levels of the three RAR mRNAs in most of the cell lines but had n o effect on the RXR mRNAs. The CRABP-II mRNA level in SqCC/Y1 cells wa s lowest in cells grown in serum-free medium and increased when the ce lls were grown in medium with 5 or 10% serum. In contrast, the RXR-alp ha mRNA level was inversely related to serum concentration. The result s show that, in head and neck squamous cell carcinoma cells, there are no simple relationships among the expression of CRABPs, RARs, and RXR s and either squamous differentiation or response to RA-induced growth inhibition or suppression of squamous differentiation.