Journal
NEOPLASIA
Volume 2, Issue 5, Pages 418-425Publisher
ELSEVIER SCIENCE INC
DOI: 10.1038/sj.neo.7900115
Keywords
inflammatory breast cancer; human mammary epithelial cells; RhoC GTPase; angiogenesis; angiogenic factors
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Funding
- NATIONAL CANCER INSTITUTE [R01CA077612, T32CA009537] Funding Source: NIH RePORTER
- NCI NIH HHS [T32 CA009537, R01 CA 77612, R01 CA077612, 5T32 CA09537 - 16] Funding Source: Medline
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Inflammatory breast cancer (IBC) is a distinct and aggressive form of locally advanced breast cancer. IBC is highly angiogenic, invasive, and metastatic at its inception. Previously, we identified specific genetic alterations of IBC that contribute to this highly invasive phenotype. RhoC GTPase was overexpressed in 90% of archival IBC 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, and studied the effect of RhoC GTPase overexpression on the modulation of angiogenesis in IBC, Levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukin-6 (IL-6), and interleukin-8 (IL-8) were significantly higher in the conditioned media of the HME-RhoC transfectants than in the untransfected HME and HME-beta -galactosidase control media, similar to the SUM149 IBC cell line. Inhibition of RhoC function by introduction of C3 exotransferase decreased production of angiogenic factors by the HME-RhoC transfectants and the SUM149 IBC cell line, but did not affect the control cells. These data support the conclusion that overexpression of RhoC GTPase is specifically and directly implicated in the control of the production of angiogenic factors by IBC cells.
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