Transformation of mammary epithelial cells by 3-phosphoinositide-dependent protein kinase-1 (PDK1) is associated with the induction of protein kinase Calpha.
Transformation of mammary epithelial cells by 3-phosphoinositide-dependent protein kinase-1 (PDK1) is associated with the induction of protein kinase Calpha.
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发表时间：
2002-06
期刊：
影响因子：
11.2
通讯作者：
Xiao Zeng;Hang-Zhong Xu;R. Glazer
中科院分区：
文献类型：
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作者：
Xiao Zeng;Hang-Zhong Xu;R. Glazer
3-磷酸肌醇依赖性蛋白激酶 1 (PDK1) 是与人类癌症中生长因子受体激活相关的多种信号传导途径的介体。为了评估 PDK1 在乳腺肿瘤发生中的作用，用 PDK1 逆转录病毒转导 COMMA-1D 小鼠乳腺上皮细胞，并通过在软琼脂中不依赖贴壁的生长来测量转化。表达 PDK1 的细胞表现出与 Akt1 激活和蛋白激酶 Cα (PKCα) 表达升高相关的高度转化。过表达 Akt1 的细胞没有表现出不依赖锚定的生长，而 PKCalpha 过表达则产生显着的转化，尽管与 PDK1 相比程度较小。 Akt1 和 PKCalpha 的共表达对转化活性产生的不仅仅是加性效应。在同系小鼠中，表达 PDK1 或 PKCα 的细胞而非表达 Akt1 的细胞的同种移植物会导致低分化乳腺癌的形成。 PDK1 在大多数人类乳腺癌细胞系中高表达。这些结果表明，PDK1 的激活可部分通过 PKCα 导致乳腺肿瘤发生，并且 PDK1 表达可能是人类乳腺癌的重要靶点。
3-Phosphoinositide-dependent protein kinase 1 (PDK1) is a mediator of multiple signaling pathways coupled to growth factor receptor activation in human cancers. To evaluate the role of PDK1 in mammary gland oncogenesis, COMMA-1D mouse mammary epithelial cells were retrovirally transduced with PDK1, and transformation was measured by anchorage-independent growth in soft agar. PDK1-expressing cells exhibited a high degree of transformation that was associated with the activation of Akt1 and an elevation of protein kinase Calpha (PKCalpha) expression. Cells overexpressing Akt1 did not exhibit anchorage-independent growth, whereas PKCalpha overexpression produced significant transformation, although to a lesser extent compared with PDK1. Coexpression of Akt1 and PKCalpha led to a more than additive effect on transformation activity. Isografts of either PDK1- or PKCalpha-expressing cells but not Akt1-expressing cells in syngeneic mice led to formation of poorly differentiated mammary carcinomas. PDK1 was highly expressed in a majority of human breast cancer cell lines. These results suggest that activation of PDK1 can lead to mammary tumorigenesis, in part through PKCalpha, and that PDK1 expression may be an important target in human breast cancer.