Proliferation mechanism of protein-free culture

无蛋白培养物的增殖机制

• 批准号: 03670696
• 负责人: CHIGIRA Masaki
• 金额: $ 1.54万
• 依托单位: Gunma University Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670696/
• 关键词: Protein-free culture; Autonomy; Calmodulin; Protein kinases; Inhibitors; Protein free culture; Autonomic proliferation; Calmodulin; Protein Kinases; Protein kinase inhibitors

We hypothesized that autonomic proliferation of tumor cells is internally programmed a priori, autocrine growth hypothesis may not be suitable to the autonomy of tumor cells in vitro. According to this hypothesis, we demonstrated that endogenous proteins secreted into the medium by protein-free cells play a negative role in the proliferation of them in general. Addition of protein kinase C inhibitor to the protein-free culture enhanced proliferation of cells, although serum-dependent proliferation were inhibited at the same concentration. From these results, external signals which stimulate cell proliferation do not play a role in the protein-free culture, although the signals included autocrine growth factors and serum. On the other hand, inhibitors against calmodulin suppressed the proliferation of protein-free cells specifically. Immunoblotting for calmodulin revealed that nuclear content of calmodulin in protein-free cells were much higher than that of serum-dependent clones. Finally, our autonomic hypothesis of proliferation has been proved.

我们假设肿瘤细胞的自主增殖是先天内部编程的，自分泌生长假说可能不适用于体外肿瘤细胞的自主性。根据这一假设，我们证明，无蛋白细胞分泌到培养基中的内源蛋白通常在它们的增殖中发挥负面作用。向无蛋白培养物中添加蛋白激酶C抑制剂增强了细胞增殖，尽管血清依赖性增殖在相同浓度下受到抑制。从这些结果来看，刺激细胞增殖的外部信号在无蛋白质培养物中不起作用，尽管信号包括自分泌生长因子和血清。另一方面，钙调蛋白抑制剂特异性抑制无蛋白细胞的增殖。钙调蛋白免疫印迹显示，无蛋白细胞中钙调蛋白的核含量远高于血清依赖性克隆。最后，我们的自主神经增殖假说得到了证明。

项目成果

M.CHIGIRA: "Development of resistance agains protein kinase inbibitor in long term protein-free culture" Int.J.Oncol. 2. 67-72 (1993)

M.CHIGIRA：“长期无蛋白培养物中对蛋白激酶抑制剂的耐药性的发展”Int.J.Oncol。

M.CHIGIKA: "A general model of carciuogenesk,(II)" Med Hypotheses.37. (1993)

M.CHIGIKA：“carciuogensk 的一般模型，（II）”医学假设.37。

M.CHIGIRA: "Developmeut of resistance agains protein kinase inhibitors in long term protein-free culture" Int.J.Oncol. 2. 67-72 (1993)

M.CHIGIRA：“长期无蛋白培养物中对蛋白激酶抑制剂的耐药性的发展”Int.J.Oncol。

H.WATANABE: "The role of endogenous proteins in the proteinーfree maintenance of three distinct tumor cell lines" Int.J.Oncol.1. 481-487 (1992)

H.WATANABE：“内源性蛋白质在三种不同肿瘤细胞系的无蛋白质维持中的作用”Int.J.Oncol.1（1992）。

M. CHIGIRA: "Origin of autonomy and anomie of tumors in cell society." Int. J. Oncol.(1993)

M. CHIGIRA：“细胞社会中肿瘤自主性和失范的起源。”