1,25(OH) 2 Vitamin D 3 induces elevated expression of the cell cycle inhibitor p18 in a squamous cell carcinoma cell line of the head and neck

• Published in: Journal of oral pathology & medicine Vol. 35; no. 8; pp. 472 - 478
• Main Authors: Gedlicka, Claudia, Hager, Gudrun, Weissenböck, Martina, Gedlicka, Wilhelm, Knerer, Birgit, Kornfehl, Johannes, Formanek, Michael
• Format: Journal Article
• Language: English
• Published: 01.09.2006
• ISSN: 0904-2512; 1600-0714
• DOI: 10.1111/j.1600-0714.2006.00407.x

Background:  1 α ,25‐Dihydroxyvitamin D 3 [1,25(OH) 2 Vitamin D 3 ] induces growth inhibition in squamous cell carcinoma (SCC) cell lines of the head and neck by arresting the cells in the G0/G1 phase of the cell cycle, probably due to an enhanced expression of p21, which could be demonstrated in other cell lines (JPPA, SCC9) before. In SCC25, a SCC cell line isolated from tongue, growth inhibition but no overexpression of p21 was detected. The retinoblastoma gene, as a direct target of G1 cyclin–CDK complexes, showed an obvious shift from the hyperphosphorylated to the hypophosphorylated form under 1,25(OH) 2 Vitamin D 3 , which indicates that the growth inhibition takes place in the G0/G1 phase. To explore the possible pathway of growth inhibition in SCC25 we investigated other cell cycle inhibitors (p18, p19, p27). Methods:  Synchronized cells were treated with 1,25(OH) 2 Vitamin D 3 over 96 h. The cell cycle status and expression of cell cycle‐regulating proteins was determined by fluorescence‐activated cell sorting (FACS) and Western blotting. Results:  An overexpression of p18 in 1,25(OH) 2 Vitamin D 3 vs. ethanol‐treated cells was determined until 30 h in SCC25. No influence was detectable on the expression of p27 and p19. Conclusion:  One mechanism by which 1,25(OH) 2 Vitamin D 3 controls cell growth might be the upregulation of p21. As p21 was unsusceptible to 1,25(OH) 2 Vitamin D 3 in SCC25, other inhibiting proteins were necessary to be tested. The proven upregulation of p18 seems to be the responsible step for growth inhibition of 1,25(OH) 2 Vitamin D 3 in SCC25.