PT  - JOURNAL ARTICLE
AU  - Zeng, Xiao
AU  - Xu, Hangmin
AU  - Glazer, Robert I.
TI  - Transformation of Mammary Epithelial Cells by 3-Phosphoinositide-dependent Protein Kinase-1 (PDK1) Is Associated with the Induction of Protein Kinase Cα
DP  - 2002 Jun 15
TA  - Cancer Research
PG  - 3538--3543
VI  - 62
IP  - 12
4099  - http://cancerres.aacrjournals.org/content/62/12/3538.short
4100  - http://cancerres.aacrjournals.org/content/62/12/3538.full
SO  - Cancer Res2002 Jun 15; 62
AB  - 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 Cα (PKCα) expression. Cells overexpressing Akt1 did not exhibit anchorage-independent growth, whereas PKCα overexpression produced significant transformation, although to a lesser extent compared with PDK1. Coexpression of Akt1 and PKCα led to a more than additive effect on transformation activity. Isografts of either PDK1- or PKCα-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 PKCα, and that PDK1 expression may be an important target in human breast cancer. ©2002 American Association for Cancer Research.