Differential effects of chromosome 3p deletion on the expression of the putative tumor suppressor RAR beta and on retinoid resistance in human squamous carcinoma cells.
Retinoids' effects on cell growth and differentiation are mediated by nuclear retinoid receptors, which are ligand-activated transcription enhancing factors. Because the expression of the retinoic acid receptor beta (RARbeta) gene, which is located on chromosome 3p24, is diminished in premalignant and malignant tissues it has been proposed that it acts as a tumor suppressor. To test the hypothesis that RARbeta loss leads to retinoid resistance, we studied several karyotyped head and neck squamous carcinoma (HNSCC) cell lines (UMSCC-17A, -17B, -22A, -22B, and -38) with deletion of one chromosome 3p arm. RARbeta mRNA was neither detected nor induced by retinoic acid in these cells, whereas it was expressed and induced by retinoic acid in two other HNSCC cell lines (1483 and 183) without 3p deletion. Methylation of the RARbeta gene promoter was detected in the 17B and 22B cells that failed to express RARbeta but no methylation was found in 183A cells that did express RARbeta mRNA. Responsiveness of HNSCC cells to several retinoids in assays of growth inhibition and colony formation, was rank ordered as: 22B>1483>38>183>17B. Additionally, retinoid response elements were transactivated in 22B more efficiently than in 17B cells. These results indicate that loss of RARbeta expression does not necessarily lead to loss of growth inhibition by retinoids or to a block of retinoid signaling.
Zou
C P
CP
Gynecologic Oncology, Department of Obstetrics, Gynecology & Reproductive Science, The University of Texas, Medical School, Houston, Texas, TX 77030, USA.
Youssef
E M
EM
Zou
C C
CC
Carey
T E
TE
Lotan
R
R
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3; D004273:DNA, Neoplasm / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D011401:Promoter Regions, Genetic; D012334:RNA, Neoplasm / Q000096:biosynthesis; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis / Q000235:genetics*; D012176:Retinoids / Q000494:pharmacology; D015533:Transcriptional Activation; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D018168:Receptors, Retinoic Acid; D012176:Retinoids; C082925:retinoic acid receptor beta; D014212:Tretinoin