Elsevier

Neoplasia

Volume 2, Issue 5, September–October 2000, Pages 418-425
Neoplasia

RhoC GTPase Overexpression Modulates Induction of Angiogenic Factors in Breast Cells1

https://doi.org/10.1038/sj.neo.7900115Get rights and content
Under a Creative Commons license
open access

Abstract

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-β-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.

Keywords

inflammatory breast cancer
human mammary epithelial cells
RhoC GTPase
angiogenesis
angiogenic factors

Abbreviations

IBC
inflammatory breast cancer
HME
human mammary epithelial cell
VEGF
vascular endothelial growth factor
bFGF
basic fibroblast growth factor
IL
interleukin

Cited by (0)

1

This work was supported by National Institutes of Health (NIH) R01 CA 77612-(S.D.M.), and NIH 5T32 CA09537-16, DOD-DAMD17-OD-1-0345 (S.D.M. and K.v.G.), and by Susan G. Komen Foundation Postdoctoral Fellowship (K.v.G.) and grant (S.D.M.).