Growth arrest of the breast cancer cell line, T47D, by TNF alpha; cell cycle specificity and signal transduction.
Growth arrest of the breast cancer cell line, T47D, by TNF alpha; cell cycle specificity and signal transduction.
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TNF Alpha对乳腺癌细胞系T47D的生长停滞；细胞周期特异性和信号转导。
DOI：
10.1038/bjc.1993.55
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发表时间：
1993-02
影响因子：
8.8
通讯作者：
MCGEE, JO
中科院分区：
文献类型：
--
作者：
PUSZTAI, L;LEWIS, CE;MCGEE, JO
本文研究了肿瘤坏死因子- α (TNF α)对人乳腺细胞株T47D生长和DNA合成的影响。在0.1 ng ml-1至100 ng ml-1的TNF α范围内，观察到胸苷结合和细胞生长的剂量依赖性，可逆性抑制。在任何实验中，细胞活力均未受损。流式细胞术DNA分析显示，暴露于TNF α 24小时后，T47D细胞在细胞周期的G1期积累，在G2/M期和S期耗尽，表明G1/S过渡的进展受到阻碍。还研究了蛋白激酶（PK）和蛋白磷酸酶在TNF α诱导的信号转导中的作用。暴露于TNF α 10分钟后，检测到总细胞蛋白激酶C （PKC）活性瞬间快速增加2倍。为了研究所观察到的PKC激活在TNF α的细胞抑制作用中的作用，将T47D细胞暴露于强效PKC抑制剂H7存在的细胞因子中。暴露于足以阻断PKC激动剂phorl -12-肉豆酸酯-13-乙酸酯（PMA）诱导的胸腺嘧啶摄取刺激的H7浓度时，TNF - α对胸腺嘧啶掺入的抑制作用不受影响。使用环核苷酸依赖性PK抑制剂H8解决了其他信号通路的参与；钙调素依赖性PK抑制剂W7；蛋白磷酸酶PP1和PP2B抑制剂冈田酸。将T47D细胞暴露于这些酶抑制剂中不能拮抗TNF α对胸腺嘧啶掺入的抑制作用。综上所述，这些结果表明TNF α对T47D细胞的细胞抑制作用发生在细胞周期的G1/S过渡阶段，并通过细胞内途径介导，该途径不涉及蛋白激酶C和A的活性，也不涉及蛋白磷酸酶PP1， PP2B的活性。
The effects of tumour necrosis factor-alpha (TNF alpha) on the growth and DNA synthesis of the human breast cell line, T47D, were studied. A dose-dependent, reversible inhibition of thymidine incorporation and cell growth was observed in the range of 0.1 ng ml-1 to 100 ng ml-1 of TNF alpha. Cell viability was not impaired in any of the experiments. Flow-cytometric DNA analysis demonstrated that after 24 h exposure to TNF alpha, T47D cells accumulated in the G1 phase of the cell cycle, and were depleted in the G2/M and S phases, suggesting a block in the progression of the G1/S transition. The involvement of protein kinases (PK) and protein phosphatases in TNF alpha-induced signal transduction was also investigated. A transient and rapid 2-fold increase in total cellular protein kinase C (PKC) activity was detected after 10 min exposure to TNF alpha. To study the role of the observed PKC activation in the cytostatic effect of TNF alpha, T47D cells were exposed to the cytokine in the presence of the potent PKC inhibitor, H7. The inhibitory effect of TNF alpha on thymidine incorporation was not affected by exposure to H7 at concentrations sufficient to block the stimulation of thymidine up-take induced by the PKC agonist, phorbol-12-myristate-13-acetate (PMA). The involvement of other signalling pathways was addressed using the cyclic nucleotide-dependent PK inhibitor, H8; the calmodulin-dependent PK inhibitor, W7; and the inhibitor of protein phosphatases PP1 and PP2B, okadaic acid. Exposure of T47D cells to these enzyme inhibitors failed to antagonise the inhibition of thymidine incorporation by TNF alpha. Taken together, these results indicate that the cytostatic effect of TNF alpha on T47D cells occurs at the G1/S transition of the cell cycle, and is mediated by an intracellular pathway which does not involve the activity of protein kinases C and A, nor protein phosphatases PP1, PP2B.
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DOI：
10.1016/0006-291x(90)91587-i
发表时间：
1990-11-15
影响因子：
3.1
作者：
LANE, TA;LAMKIN, GE;WANCEWICZ, EV
通讯作者：
WANCEWICZ, EV
影响因子：
3.5
作者：
MANTOVANI, L;HENSCHLER, R;HERRMANN, F
通讯作者：
HERRMANN, F
影响因子：
2.9
作者：
HIDAKA, H;INAGAKI, M;SASAKI, Y
通讯作者：
SASAKI, Y
影响因子：
3.8
作者：
FEUILLARD, J;GOUY, H;KORNER, M
通讯作者：
KORNER, M
影响因子：
3.5
作者：
MANTOVANI, L;HENSCHLER, R;HERRMANN, F
通讯作者：
HERRMANN, F