Expression of retinoic acid receptor beta is associated with inhibition of keratinization in human head and neck squamous carcinoma cells.

Abstract

The preventive effects of retinoids on oral carcinogenesis may be related to their ability to modulate the growth and differentiation of human oral squamous epithelial cells. Nuclear retinoid receptors (RAR alpha, beta, and gamma, and RXR alpha, beta, and gamma) may mediate these effects by regulating gene transcription. The removal of serum from the growth medium of two head and neck squamous cell carcinoma lines 1483 and SqCC/Y1 resulted in a decrease in RAR beta mRNA level and concurrent increases in the expression of the keratin K1 and transglutaminase type I (TGase I), which are markers of differentiation of keratinizing squamous epithelial cells. All-trans-retinoic acid (tRA) or 13-cis-RA increased RAR beta and decreased K1 and TGase I mRNA levels in serum-free medium. Transcriptional activation of reporter genes by means of retinoid response elements (RARE and RXRE) indicated that the RXR-RAR pathway predominates over the RXR homodimer pathway in the 1483 cells. Among several synthetic retinoids with preference for binding to specific nuclear retinoid receptors, those that induced RAR beta also suppressed K1. The inverse association between RAR beta expression and K1 and TGase I levels implicates this receptor in suppression of keratinization in oral epithelial cells.

• Authors: C P Zou, W K Hong, R Lotan
• Journal: Differentiation; research in biological diversity (Differentiation) Vol. 64 Issue 2 Pg. 123-32 (Jan 1999) ISSN: 0301-4681 [Print] England
• PMID: 10234809 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Biomarkers, Tumor
• CD 437
• Receptors, Retinoic Acid
• Retinoid X Receptors
• Retinoids
• Transcription Factor AP-1
• Transcription Factors
• retinoic acid receptor beta
• Tretinoin
• Keratins
• Collagenases

Topics

• Biomarkers, Tumor (analysis)
• Carcinoma, Squamous Cell (drug therapy, metabolism)
• Cell Differentiation (physiology)
• Cell Division (drug effects)
• Collagenases (drug effects, genetics, metabolism)
• Dose-Response Relationship, Drug
• Gene Expression Regulation, Neoplastic (drug effects)
• Head and Neck Neoplasms (drug therapy, metabolism)
• Humans
• Keratins (drug effects, metabolism)
• Promoter Regions, Genetic
• Receptors, Retinoic Acid (antagonists & inhibitors, drug effects, genetics, metabolism)
• Response Elements (drug effects)
• Retinoid X Receptors
• Retinoids (pharmacology)
• Transcription Factor AP-1 (genetics, metabolism)
• Transcription Factors (drug effects, genetics)
• Transcription, Genetic
• Transcriptional Activation
• Tretinoin (metabolism, pharmacology)
• Tumor Cells, Cultured (drug effects, metabolism)