Effects of Intracellular Calcium on Cell Survival and the MAPK Pathway in a Human Hormone‐Dependent Leukemia Cell Line (TF‐1)

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Abstract
Changes in the cytoplasmic calcium concentration ([Ca2+]i) regulate a wide variety of cellular processes. Here we demonstrate that increased [Ca2+]i was able to induce hormone‐independent survival and proliferation, as well as to evoke apoptosis in human myelo‐erythroid GM‐CSF/IL‐3 dependent leukemia cells (TF‐1). Cellular responses induced by elevated [Ca2+]i depended on the duration and amplitude of the calcium‐signal. Moderate or high, but transient, elevation of [Ca2+]i caused a transient, biphasic activation of ERK1/2 and protected cells from hormone withdrawal‐induced apoptosis. 1 In contrast, high and long‐lasting elevation of [Ca2+]i led to sustained activation of the ERK1/2 kinases and apoptosis of TF‐1 cells. Our data suggest that a time‐dependent action of the MAPK pathway works as a decision‐point between cell proliferation and apoptosis.