Differential effects of chromosome 3p deletion on the expression of the putative tumor suppressor RARβ and on retinoid resistance in human squamous carcinoma cells

Abstract

Retinoids' eects on cell growth and dierentiation are mediated by nuclear retinoid receptors, which are ligandactivated transcription enhancing factors. Because the expression of the retinoic acid receptor b (RARb) 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 RARb 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. RARb 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 RARb gene promoter was detected in the 17B and 22B cells that failed to express RARb but no methylation was found in 183A cells that did express RARb mRNA. Responsiveness of HNSCC cells to several retinoids in assays of growth inhibition and colony formation, was rank ordered as: 22B414834384183417B. Additionally, retinoid response elements were transactivated in 22B more eciently than in 17B cells. These results indicate that loss of RARb expression does not necessarily lead to loss of growth inhibition by retinoids or to a block of retinoid signaling. Oncogene (2001) 20, 6820 ± 6827.

Hypermethylation and Silencing of the Putative Tumor SuppressorTazarotene-Induced Gene 1in Human Cancers

“…On the other hand, similar treatment of cell lines that exhib- ited basal expression of TIG1 resulted in a significant induction of expression. In a previous study (22), we observed the same pattern in the inducibility of RAR␤2 expression, which occurred only in cell lines that had at least some basal endogenous expression of RAR␤2. These data suggest that individual cell lines with a minimum endogenous level of TIG1 expression exhibit an increase in expression after retinoic acid treatment.…”

High Serum Level of Retinol and α-Tocopherol Affords Protection Against Oral Cancer in a Multiethnic Population

“…The protective effect exerted by retinol and α-tocopherol could be explained by their role as potent regulators of cellular activities, thus having significant impact on oral carcinogenesis (Mukherjee et al, 2011). These micronutrients are also strong antioxidants that have been shown to suppress the development of malignancy in cell culture experiments and animal studies (Zou et al, 2001). Although the mechanism of action is rather complex and unclear, it has been hypothesized that antioxidant activity of these micronutrients prevents tissue damage by deactivating excited oxygen molecules and neutralizing free radicals (Poljsak, 2007) which then translates into the protective effects seen.…”

Genetic or epigenetic silencing of low density lipoprotein receptor‐related protein 1B expression in oral squamous cell carcinoma

“…(8) Although several genes, for example, p14, p15, p16, RASSF1A, VHL, hMLH1, and MGMT, have been reported to be silenced by aberrant DNA methylation, (9)(10)(11)(12)(13)(14)(15)(16) some of them were infrequently methylated in OSCC compared with other tumors. In order to create the b.est possible panel of markers for the prediction of outcome, sensitivity to chemotherapy and radiation, and disease status OSCC, more candidates for tumor-suppressor genes targeted by promoter methylation will no doubt be tested in this disease.…”