Calcium dependency in the growth of adult T-cell leukemia cells in vitro.
The effects of calcium, calcium antagonists, and calmodulin inhibitors on the growth of adult T-cell leukemia (ATL) cells were studied in vitro. Fresh ATL cells from patients and established ATL cell lines did not grow well in a low-calcium (less than 0.01 mM) medium. However, their growth was enhanced by the addition of calcium to the medium in a dose-dependent manner. The maximum response was induced at 4 mM calcium, which was higher than that of the normal serum calcium level, 2.5 mM. Other leukemia cells, except ATL, grew well in the low-calcium medium, and their growth was not enhanced by the addition of calcium. Calcium antagonists and calmodulin inhibitors inhibited the growth of ATL cells at the concentration of 10(-5)-10(-7) M, while they did not inhibit the growth of other leukemia cells. Furthermore, the expression of interleukin 2 receptors (Tac antigens) on ATL cells was also enhanced by calcium and was inhibited by calcium antagonists and calmodulin inhibitors. In accordance with these results, the increase of the extracellular calcium concentration resulted in the increase of the intracellular calcium concentration in ATL cells, but not in other leukemia cells. These results suggest that calcium and calmodulin play a critical role in regulating the growth of ATL cells.
Shirakawa
F
F
Yamashita
U
U
Oda
S
S
Chiba
S
S
Eto
S
S
Suzuki
H
H
D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D003593:Cytoplasm / Q000502:physiology; D004247:DNA / Q000096:biosynthesis; D006800:Deltaretrovirus Infections / Q000473:pathology*; D005110:Extracellular Space / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000187:drug effects
D002121:Calcium Channel Blockers; D002147:Calmodulin; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D004247:DNA; D002118:Calcium