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- W2076469466 abstract "Receptor-activated transmembrane calcium flux has been implicated as a mediator of the actions of many growth factors and hormones. We examined the effects of PRL, calcium ionophores, and calcium antagonists on 45Ca2+ flux, c-myc gene expression, and DNA synthesis in the PRL-dependent rat Nb2 lymphoma cell line. PRL had no detectable effects on 45Ca2+ uptake or efflux, and the mitogenic effects of PRL could not be reproduced by the calcium ionophore A23187 alone or in combination with the tumor-promoting phorbol ester 12-O-tetradecanoyl- phorbol-13 acetate (TPA). PRL, but not A23187 or TPA, stimulated c-myc gene expression in quiescent Nb2 cells. Exposure to PRL for brief periods (15 min to 4 h), followed by extensive washing, resulted in a time- and dose-dependent activation of DNA synthesis measured 16 h later. This activation was not blocked by addition of excess anti-PRL antiserum after the wash steps, indicating that the observed stimulation was not due to residual PRL. Despite the marked increase in DNA synthesis, removal of PRL after 4 h prevented mitosis, suggesting that PRL may be required throughout the cell cycle for Nb2 cell proliferation. Although continuous incubation with calcium antagonists resulted in a dose-dependent inhibition of PRLstimulated DNA synthesis, activation of DNA synthesis by brief exposure to PRL was not inhibited by the presence of EGTA, calcium channel blockers (nifedipine, cobalt chloride), or calmodulin inhibitors (trifluoperazine, AT-6-aminohexyl-5-chloronaphthalene sulfonamide). PRL-stimulated c-myc expression was attenuated, but not blocked, by the calcium channel antagonists. However, the putative intracellular calcium antagonist TMB-8 inhibited both c-myc expression and DNA synthesis in a dose-dependent manner (IC50 = 16 μM). Nb2 cells were sensitive to TMB-8 throughout G1 of the cell cycle, but inhibition of DNA synthesis was greatest when TMB-8 was present during the first 3 h of mitogen presentation, indicating a block in the transition from G0 to G1 of the cell cycle. The effect of TMB-8 suggests that release of a small intracellular calcium pool may mediate the early actions of PRL in Nb2 cells. (Endocrinology122: 2476–2485,1988)" @default.
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- W2076469466 date "1988-06-01" @default.
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- W2076469466 title "Role of Calcium in Prolactin-Stimulated c-<i>myc</i>Gene Expression and Mitogenesis in NB2 Lymphoma Cells*" @default.
- W2076469466 doi "https://doi.org/10.1210/endo-122-6-2476" @default.
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