Differences of cell growth and cell cycle regulators induced by basic fibroblast growth factor between nifedipine responders and non-responders.
Differences of cell proliferation, cell cycle, and G(1)/S transition regulatory proteins of gingival fibroblasts derived from nifedipine-reactive patient (NIFr) and nifedipine-non-reactive patient (NIFn) in the presence of basic fibroblast growth factor (bFGF) were investigated to elucidate the mechanism of gingival overgrowth associated with nifedipine, one of the Ca(2+)-channel blockers. The proliferation rate of NIFr cells in the presence of bFGF significantly increased than NIFn cells. The proportion of NIFr cells that had undergone progression to the S and G(2)/M phases from the G(0)/G(1) phase significantly increased compared to that in NIFn cells. Increases of pRB (Ser807/811), pCDK2 (Thr160), CDK2, and cyclin E protein levels in NIFr cells were greater than those in NIFn cells. The elevations of pRB (Ser780), RB, and cyclin A protein levels in NIFr cells did not differ from those of NIFn cells. The growth of NIFr cells was greater than that of NIFn cells as a result of the active G(1)/S transition of NIFr cells, as assessed by the increments of cyclin E, pCDK2, and pRB (ser807/811) protein in NIFr cells.
Takeuchi
Reiri
R
Department of Oral Molecular Pharmacology, Nihon University School of Dentistry at Matsudo, 2-870-1 Sakaecho-Nishi, Matsudo, Chiba 271-8587, Japan.
Matsumoto
Hiroko
H
Okada
Hidehiko
H
Hori
Mami
M
Gunji
Akihiko
A
Hakozaki
Kosuke
K
Akimoto
Yoshiaki
Y
Fujii
Akira
A
D000963:Antimetabolites; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects; D005881:Gingiva / Q000166:cytology; D006801:Humans; D009543:Nifedipine / Q000494:pharmacology*; D016196:S Phase / Q000187:drug effects
D000963:Antimetabolites; D002121:Calcium Channel Blockers; D018797:Cell Cycle Proteins; D016222:Fibroblast Growth Factor 2; D004247:DNA; D001973:Bromodeoxyuridine; D009543:Nifedipine