The oncogenic role of androgen receptors in promoting the growth of oral squamous cell carcinoma cells

• Published in: Oral diseases Vol. 21; no. 3; pp. 320 - 327
• Main Authors: Wu, T-F, Luo, F-J, Chang, Y-L, Huang, C-M, Chiu, W-J, Weng, C-F, Hsu, Y-K, Yuan, T-C
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.04.2015; Wiley Subscription Services, Inc
• Subjects: Androgen Antagonists - pharmacology; androgen receptor; Androgens; Androgens - pharmacology; Anilides - pharmacology; Animals; Apoptosis; bicalutamide; Carcinoma, Squamous Cell - chemistry; Carcinoma, Squamous Cell - pathology; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Proliferation - genetics; Cell Transformation, Neoplastic - genetics; Cyclin D1 - drug effects; Cyclin D1 - metabolism; Dentistry; dihydrotestosterone; Dihydrotestosterone - pharmacology; Gene Knockdown Techniques; Humans; Medical research; Mice; Mouth Neoplasms - chemistry; Mouth Neoplasms - pathology; Nitriles - pharmacology; Oral cancer; oral squamous cell carcinoma; Precancerous Conditions - chemistry; Proteins; Receptors, Androgen - analysis; Receptors, Androgen - genetics; Receptors, Androgen - metabolism; Tosyl Compounds - pharmacology; Tumors; cell growth; oral squamous cell carcinoma; androgen receptor; dihydrotestosterone; bicalutamide
• ISSN: 1354-523X; 1601-0825
• DOI: 10.1111/odi.12272

Objectives The aims of this study were to examine the expression of androgen receptors (AR) in oral squamous cell carcinoma (OSCC) cells and tumors and to determine the role of AR in regulating OSCC cell growth. Materials and Methods Four OSCC cell lines were used for analyzing AR expression and transcriptional activity. The effects of AR knockdown on the growth and tumorigenicity of OSCC cells were examined. A series of 11 benign, 22 premalignant, and 21 malignant lesions of the oral cavity were used for analyzing AR expression. Results OSCC cells expressed AR proteins with differential activities. Stimulation of AR by dihydrotestosterone in OSCC cells caused an increase in cyclin D1 expression and promoted cell growth, whereas treatment with bicalutamide led to decreased cyclin D1 expression and inhibited cell growth. Knockdown of AR expression in OSCC cells resulted in decreased proliferation, increased apoptosis, and inhibited tumorigenicity. Results from immunohistochemical studies showed that AR immunoreactivity was found in 27% (3/11) of benign lesions, while 68% (15/22) of premalignant and 67% (14/21) of malignant lesions showed positive AR staining. Conclusion Our data suggest that OSCC cells express functional AR proteins which are critical for promoting cell growth and causing malignant disease.