Inhibition of cancer cell growth by all-trans retinoic acid and its analog N-(4-hydroxyphenyl) retinamide: a possible mechanism of action via regulation of retinoid receptors expression.
In order to better understand the mechanisms that underlie the antiproliferative effect of retinoids, we have examined the response of human carcinoma cell lines to all-trans retinoic acid (RA) and N-(4-hydroxyphenyl) retinamide (4HPR) in terms of cell growth, apoptosis and regulation of retinoic acid receptors (RARs) and retinoid X receptors (RXRs) mRNA. GLC82 (lung adenocarcinoma), BGC823 (stomach adenocarcinoma) and EC109 (esophageal squamous carcinoma) cells were treated with 10 microM of RA or 4HPR for various length of time and analyzed. The results show that growth inhibition by RA and 4HPR in GLC82 and BGC823 cells correlates with the induction of RARbeta2 gene, whereas RA resistance in EC109 cells parallels loss of RARbeta2 induction. Exogenous RARbeta2 expression did not restore RA responsiveness in EC109 cells, but potentiated 4HPR-induced growth inhibition, suggesting that 4HPR acts at least in part via the RARbeta receptor. We speculate that the loss of RARbeta2 inducibility in EC109 cells may be due to an unknown repressor.
Liu
G
G
Laboratory of Molecular Oncology, Cancer Institute, CAMS and PUMC, Beijing, China.
Wu
M
M
Levi
G
G
Ferrari
N
N
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000473:pathology; D017313:Fenretinide / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000648:ultrastructure; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D047488:Retinoid X Receptors; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; C082925:retinoic acid receptor beta; D017313:Fenretinide; D014212:Tretinoin