4.8 Article

Choline kinase activation is a critical requirement for the proliferation of primary human mammary epithelial cells and breast tumor progression

Journal

CANCER RESEARCH
Volume 64, Issue 18, Pages 6732-6739

Publisher

AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-04-0489

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Breast cancer is still one of the most important tumors among women in industrialized countries. Improvement in both understanding the molecular events associated with the disease and the development of new additional treatments is still an important goal to be achieved. Cholme kinase (ChoK) is increased in human mammary tumors with high incidence, and this activation is associated with clinical variable indicators of greater malignancy. Here, we have investigated the role of ChoK in the development of breast cancer and found that Cholk is both necessary and suflicient for growth factor-induced proliferation in primary human mammary epithelial cells and an absolute requirement for the specific mitogenic response to heregulin in breast tumor-derived cells. These results demonstrate that ChoK plays an essential role in both norma human mammary epithelial cell proliferation and breast tumor progression. Furthermore, inhibition of Cholk shows a strong in vivo antitumor activity against human breast cancer xenografts. Thus, ChoK constitutes a novel bona fide molecular target for the treatment of breast cancer patients.

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