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[Cancer Research 60, 5832-5838, October 15, 2000]
© 2000 American Association for Cancer Research

Tumor Biology

RhoC GTPase, a Novel Transforming Oncogene for Human Mammary Epithelial Cells That Partially Recapitulates the Inflammatory Breast Cancer Phenotype1

Kenneth L. van Golen, Zhi-Fen Wu, Xiao Tan Qiao, Li Wei Bao and Sofia D. Merajver2

Department of Internal Medicine, Division of Hematology and Oncology and Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109

Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer and is phenotypically distinct from other forms of locally advanced breast cancer. In a previous study, we identified specific genetic alterations of IBC that could account for a highly invasive phenotype. RhoC GTPase was overexpressed in 90% of IBC archival tumor samples, but not in stage-matched, non-IBC tumors. To study the role of RhoC GTPase in contributing to an IBC-like phenotype, we generated stable transfectants of human mammary epithelial cells overexpressing the RhoC gene. The HME-RhoC transfectants formed large colonies under anchorage-independent growth conditions, were more motile, and were invasive. In conjunction with an increase in motility, overexpression of RhoC led to an increase in actin stress fiber and focal adhesion contact formation. Furthermore, orthotopic injection into immunocompromised mice led to tumor formation. Taken together, these data indicate that RhoC GTPase is a transforming oncogene in human mammary epithelial cells and can lead to a highly invasive phenotype, akin to that seen in IBC.




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