Buckley A R, Montgomery D W, Kibler R, Putnam C W, Zukoski C F, Gout P W, Beer C T, Russell D H
Immunopharmacology. 1986 Aug;12(1):37-51. doi: 10.1016/0162-3109(86)90050-0.
The tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with calcium ionophores has been shown to bypass the requisite antigen- or lectin-induced signal for lymphocyte mitogenesis. This suggests that protein kinase C activation and calcium mobilization may be early events required for lymphocyte proliferation. Therefore, the relationship(s) of protein kinase C activation and calcium mobilization to ornithine decarboxylase induction and cellular proliferation were examined in a rat node lymphoma cell line (Nb2) which is dependent upon prolactin (PRL) for mitogenesis. TPA enhanced PRL-stimulated Nb2 node lymphoma cell ornithine decarboxylase induction and [3H]thymidine incorporation. Addition of a calcium ionophore (A23187) to cultures containing TPA plus PRL increased ornithine decarboxylase above PRL alone or PRL plus TPA but inhibited proliferation compared to the PRL plus TPA regimen. Exposure of cells to TPA or TPA plus A23187 increased [3H]thymidine incorporation in a similar manner to that demonstrated for low-dose PRL. However, optimal concentrations were only 20-25% as effective as mitogens as was optimal PRL. Protein kinase C and calmodulin antagonists inhibited PRL-stimulated ornithine decarboxylase induction and proliferation. Ca2+ chelation or cation channel antagonism inhibited both PRL-stimulated responses. The cyclic AMP analogue, 8Br-cAMP, inhibited PRL-stimulated ornithine decarboxylase activity as well as cellular proliferation processes assessed by [3H]thymidine incorporation. Finally, tumor-promoting phorbol esters inhibited 125I-rPRL binding. These data strongly suggest that protein kinase C activation and calcium mobilization are requisite events for PRL-stimulated ornithine decarboxylase induction and cellular proliferation in Nb2 node lymphoma cells. An additional component that is linked to alterations in K+ channeling is also implicated. These data support a role for protein kinase C in PRL-coupled mitogenesis. However, other critical Ca2+ and/or ion-induced events are also required.
肿瘤促进剂12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）与钙离子载体联合使用已被证明可绕过淋巴细胞有丝分裂所需的抗原或凝集素诱导信号。这表明蛋白激酶C激活和钙动员可能是淋巴细胞增殖所需的早期事件。因此，在依赖催乳素（PRL）进行有丝分裂的大鼠淋巴结淋巴瘤细胞系（Nb2）中，研究了蛋白激酶C激活和钙动员与鸟氨酸脱羧酶诱导及细胞增殖之间的关系。TPA增强了PRL刺激的Nb2淋巴结淋巴瘤细胞鸟氨酸脱羧酶的诱导和[³H]胸苷掺入。在含有TPA加PRL的培养物中添加钙离子载体（A23187），使鸟氨酸脱羧酶水平高于单独使用PRL或PRL加TPA时，但与PRL加TPA方案相比，抑制了细胞增殖。细胞暴露于TPA或TPA加A23187时，[³H]胸苷掺入的增加方式与低剂量PRL的情况相似。然而，最佳浓度的效果仅为有丝分裂原最佳PRL的20 - 25%。蛋白激酶C和钙调蛋白拮抗剂抑制PRL刺激的鸟氨酸脱羧酶诱导和细胞增殖。Ca²⁺螯合或阳离子通道拮抗作用抑制了PRL刺激的两种反应。环磷酸腺苷类似物8Br - cAMP抑制PRL刺激的鸟氨酸脱羧酶活性以及通过[³H]胸苷掺入评估的细胞增殖过程。最后，促肿瘤佛波酯抑制¹²⁵I - rPRL结合。这些数据强烈表明，蛋白激酶C激活和钙动员是PRL刺激的Nb2淋巴结淋巴瘤细胞中鸟氨酸脱羧酶诱导和细胞增殖的必要事件。还涉及与钾离子通道改变相关的另一个成分。这些数据支持蛋白激酶C在PRL偶联的有丝分裂中的作用。然而，其他关键的Ca²⁺和/或离子诱导事件也是必需的。
