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

Abstract

Many lung cancer cell lines are resistant to the growth inhibitory eects of retinoids. However, some small-cell lung cancer cell lines were inhibited by all trans-retinoic acid (ATRA) in serum-free medium. We compared the responses of seven non-small cell lung cancer (NSCLC) cell 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 serumfree medium, the growth of the Calu-1 cell line was stimulated by ATRA in a dose-dependent fashion with a maximum at 10 78 M. Delipidized serum (42.5%) but not bovine serum albumin (0.15%) suppressed growth stimulation by ATRA. Transcripts of RA receptors RARa and RARg but not of RARb were detected in Calu-1 cells. Receptor expression, the formation of a complex among receptors and a RA-responsive element (RARE), and the transcriptional activation RARE were not suppressed by serum. Natural retinoids and synthetic receptor class-or subtype-selective retinoid agonists, which activated RARs and RXRs 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 serum-free medium but not in serum-containing medium. Both ATRA and CD2366 enhanced the transcriptional activation of an Activator Protein-1 (AP-1)-luciferase reporter construct in serum-free medium but not in delipidized serum. Transcriptional activation of the RARE by ATRA occurred both in the presence or absence of delipidized serum. These results demonstrate that retinoid-induced growth stimulation of Calu-1 cells is associated with enhanced AP-1 transactivation but not with RARE transactivation.

Down‐regulation of the diphthamide biosynthesis protein 2like gene during retinoid‐induced differentiation and apoptosis: Implications against its tumor‐suppressor activity

“…3) (Li et al, 1998) cells, and DPH2L is concomitantly down-regulated during treatment. 3) (Wan et al, 1997;Lee et al, 1997), we observed down-regulation of DPH2L in response to 4HPR but not to all-trans RA. 3) (van der Leede et al, 1993), DPH2L remained constant after these treatments.…”

Differential response of human fetal smooth muscle cells from arterial duct to retinoid acid

“…After RA treatment, the signal intensity was enhanced to 175.33±10.80 (P<0.05, n=6; Figure 2A,2B,2G). Together with CD2366, a RA receptor-selective antagonist [16] , the induction of PCNA by RA expression was overcome. There were no differences of the PCNA expression levels among the control, CD and RA+CD groups.…”

Transient modulation of cytoplasmic and nuclear retinoid receptors expression in differentiating human teratocarcinoma NT2 cells

“…Retinoids can exert different, and even opposite effects on cell proliferation and differentiation depending on the dose, the cellular context and experimental conditions employed (Wan et al . 1997).…”

“…Retinoids can exert different, and even opposite effects on cell proliferation and differentiation depending on the dose, the cellular context and experimental conditions employed (Wan et al 1997). The only differentiative effects of 4HPR were reported in long-term cultures of F9 cells surviving treatment with 1-10 lM 4HPR, which displayed a parietal endoderm morphology resembling RA-treated cells (Clifford et al 1999), and in oesophageal squamous carcinoma cell lines (Muller et al 1997).…”