title: 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 effects 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 serum-free medium, the growth of the Calu-1 cell line was stimulated 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%) suppressed growth stimulation by ATRA. Transcripts of RA receptors RARalpha and RARgamma but not of RARbeta 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.
authors.affiliation: Department of Tumor Biology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: H
authors.initials: H
authors.lastname: Wan
authors.forename: M I
authors.initials: MI
authors.lastname: Dawson
authors.forename: W K
authors.initials: WK
authors.lastname: Hong
authors.forename: R
authors.initials: R
authors.lastname: Lotan
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry; D016895:Culture Media, Serum-Free; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D009363:Neoplasm Proteins / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D012176:Retinoids / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D001565:Benzoates; D003470:Culture Media; D016895:Culture Media, Serum-Free; D009363:Neoplasm Proteins; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D013764:Tetrahydronaphthalenes; D018808:Transcription Factor AP-1; C088338:SR 11217; C097595:SR 11234; D014212:Tretinoin