ENHANCEMENT OF CALU-1 HUMAN LUNG-CARCINOMA CELL-GROWTH IN SERUM-FREE MEDIUM BY RETINOIDS - DEPENDENCE ON AP-1 ACTIVATION, BUT NOT ON RETINOID RESPONSE ELEMENT ACTIVATION

Many lung cancer cell lines are resistant to the growth inhibitory eff ects of retinoids, However, some small-cell lung cancer cell lines wer e inhibited by all trans-retinoic acid (ATRA) in serum-free medium, We compared the responses of seven non-small cell lung cancer (NSCLC) ce ll lines to ATRA in serum-free medium and in medium supplemented with delipidized serum, Whereas the growth of four cell lines was inhibited more in serum-free medium, the growth of the Calu-1 cell line was sti mulated by ATRA in a dose-dependent fashion with a maximum at 10(-8) M . Delipidized serum (>2.5%) but not bovine serum albumin (0.15%) suppr essed growth stimulation by ATRA, Transcripts of RA receptors RAR alph a and RAR gamma but not of RAR beta were detected in Calu-1 cells, Rec eptor expression, the formation of a complex among receptors and a RA- responsive element (RARE), and the transcriptional activation RARE wer e not suppressed by serum, Natural retinoids and synthetic receptor cl ass-or subtype-selective retinoid agonists, which activated RARs and R XRs for gene transcription from a RARE, and a RAR antagonist (CD2366), which was unable to do so, stimulated the growth of Calu-1 cells in s erum-free medium but not in serum-containing medium, Both ATRA and CD2 366 enhanced the transcriptional activation of an Activator Protein-1 (AP-1)-luciferase reporter construct in serum-free medium but not in d elipidized serum, Transcriptional activation of the RARE by ATRA occur red both in the presence or absence of delipidized serum, These result s demonstrate that retinoid-induced growth stimulation of Calu-1 cells is associated with enhanced AP-1 transactivation but not with RARE tr ansactivation.