1,25(OH)2Vitamin D3 induces elevated expression of the cell cycle inhibitor p18 in a squamous cell carcinoma cell line of the head and neck

Autor: Gudrun Hager, Claudia Gedlicka, Birgit Knerer, Wilhelm Gedlicka, Martina Weissenböck, Johannes Kornfehl, Michael Formanek
Rok vydání: 2006
Předmět:
Zdroj: Journal of Oral Pathology and Medicine. 35:472-478
ISSN: 1600-0714
0904-2512
DOI: 10.1111/j.1600-0714.2006.00407.x
Popis: BACKGROUND: I α,25-Dihydroxyvitamin D 3 [I,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/GI 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 p2I was detected. The retinoblastoma gene, as a direct target of G I cyclin-CDK complexes, showed an obvious shift from the hyperphosphorylated to the hypophosphorylated form under I,25(OH) 2 Vitamin D 3 , which indicates that the growth inhibition takes place in the G0/GI phase. To explore the possible pathway of growth inhibition in SCC25 we investigated other cell cycle inhibitors (pI8, pI9, p27). METHODS: Synchronized cells were treated with I,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 pI8 in I,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 pI9. CONCLUSION: One mechanism by which I,25(OH) 2 Vitamin D 3 controls cell growth might be the upregulation of p2I. As p2I was unsusceptible to I,25(OH) 2 Vitamin D 3 in SCC25, other inhibiting proteins were necessary to be tested. The proven upregulation of pI8 seems to be the responsible step for growth inhibition of I,25(OH) 2 Vitamin D 3 in SCC25.
Databáze: OpenAIRE