蛋白激酶C的过度生产导致大鼠纤维细胞的生长控制失调
G M Housey1, M D Johnson, W L Hsiao
1Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Cell
|February 12, 1988
概括
在老鼠细胞中过度表达蛋白激酶C (PKC) 导致了显著的生长异常,包括对瘤促进物的增强反应. 这表明PKC激活对于细胞生长控制和多阶段致癌是至关重要的.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 蛋白激酶C (PKC) 是一种参与各种细胞过程的酶家族.
- 已知瘤促进剂,如12-O-tetradecanoyl phorbol-13-acetate (TPA),可以激活PKC.
- 单个PKC异型在细胞生长和致癌过程中的确切作用仍然不完全理解.
研究的目的:
- 在大鼠纤维细胞细胞系中研究过度表达PKC的β1形式的功能后果.
- 为了确定单独增加PKC活性是否足以诱导异常细胞生长.
- 阐明PKC在调解细胞对博激素瘤促进物的反应中的作用.
主要方法:
- 生成稳定的大鼠纤维细胞细胞系,过度表达全长β 1 PKC cDNA.
- 在工程细胞系中测量PKC活性.
- 在单层和软培养物中评估形态变化和生长特征.
- 细胞暴露于TPA以评估反应.
主要成果:
- 过度表达PKC的细胞显示PKC活性增加了20-53倍.
- 这些细胞在暴露于TPA时显示出增强的形态变化和增加的和密度.
- 过度表达的PKC赋予了软,无论是带有TPA还是没有TPA,在软中独立于固的生长.
- 过度生产PKC导致大鼠纤维细胞的多种生长异常.
结论:
- 过度生产β1 PKC足以诱导大鼠纤维细胞的显著生长异常.
- PKC在细胞生长控制中起着至关重要的作用.
- PKC调解了博乙烯瘤促进体的关键细胞效应.
- PKC激活可能是多阶段致癌的核心.
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