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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
Author(s) -
Gedlicka Claudia,
Hager Gudrun,
Weissenböck Martina,
Gedlicka Wilhelm,
Knerer Birgit,
Kornfehl Johannes,
Formanek Michael
Publication year - 2006
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/j.1600-0714.2006.00407.x
Subject(s) - head and neck , cell culture , basal cell , cell , head and neck squamous cell carcinoma , cell cycle , cancer research , medicine , pathology , chemistry , biology , head and neck cancer , cancer , biochemistry , genetics , surgery
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.