Differences of Cell Growth and Cell Cycle Regulators Induced by Basic Fibroblast Growth Factor Between Nifedipine Responders and Non-responders

Abstract

Differences of cell proliferation, cell cycle, and G₁/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 Ca²⁺-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 G₂/M phases from the G₀/G₁ 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 G₁/S transition of NIFr cells, as assessed by the increments of cyclin E, pCDK2, and pRB (ser807/811) protein in NIFr cells.