ALTERED CALCIUM REGULATION IN SV40-TRANSFORMED SWISS 3T3 FIBROBLASTS

Calcium homeostasis has long been thought to be altered in transformed cells but mechanisms have not been established. In this study, the ph otoprotein, aequorin, was used to examine calcium regulation in 3T3 an d SV40-transformed 3T3 cells. It was found that calcium transients ind uced by bradykinin or serum in serum-starved cells are lower and delay ed in the transformed cells and decay kinetics are altered. These chan ges are not related to differences in cell cycle distribution. Though the serum transient is insensitive to nifedipine, verapamil, or lantha num, removal of extracellular calcium accelerates transient decay in b oth cell types. Treatment of unstimulated cells with the ER Ca2+-ATPas e inhibitor, thapsigargin, causes a 4-5-fold greater increase in [Ca2]i in the transformed than in the nontransformed cells. Following seru m stimulation, transformed cells still exhibit a large thapsigargin-in duced increase in [Ca2+], whereas the response in nontransformed cells is nearly abolished. When the 3T3 or SV3T3 cells are exposed to serum or thapsigargin in the absence of extracellular calcium and subsequen tly exposed to 11.8 mM Ca2+, a much greater influx of calcium again oc curs in the SV3T3 cells. The observed changes in SV3T3 cells are most likely due to an alteration in a capacitative mechanism which regulate s influx of calcium through the plasma membrane.