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神经增殖是先验的，自分泌生长假设可能不适用于体外肿瘤细胞的自主权。根据这一假设，我们证明了无蛋白质细胞分泌到培养基中的内源性蛋白在通常的增殖中起负面作用。在无蛋白质培养物中添加蛋白激酶C抑制剂增强了细胞的增殖，尽管在相同的浓度下抑制了血清依赖性增殖。从这些结果中，刺激细胞增殖的外部信号在无蛋白质培养中不起作用，尽管这些信号包括自分泌生长因子和血清。另一方面，针对钙调蛋白的抑制剂特别抑制了无蛋白质细胞的增殖。钙调蛋白的免疫印迹表明，无蛋白质细胞中钙调蛋白的核含量远高于血清依赖性克隆的核含量。最后，我们已经证明了我们的自主性假设。

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。”