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.
BACKGROUND
1Alpha,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. 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.


CONCLUSIONS
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.
Gedlicka
Claudia
C
Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Vienna, Austria. claudia.gedlicka@meduniwien.ac.at
Hager
Gudrun
G
Weissenböck
Martina
M
Gedlicka
Wilhelm
W
Knerer
Birgit
B
Kornfehl
Johannes
J
Formanek
Michael
M
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000378:metabolism*; D050764:Cyclin-Dependent Kinase Inhibitor p19 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D016193:G1 Phase / Q000502:physiology; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D011817:Rabbits; D016192:Resting Phase, Cell Cycle / Q000502:physiology; D014062:Tongue Neoplasms / Q000378:metabolism / Q000473:pathology
C493971:CDKN2C protein, human; D050763:Cyclin-Dependent Kinase Inhibitor p18; D050764:Cyclin-Dependent Kinase Inhibitor p19; D009363:Neoplasm Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D002117:Calcitriol