title: RhoC GTPase overexpression modulates induction of angiogenic factors in breast cells.
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-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.
authors.affiliation: Department of Internal Medicine, The University of Michigan Comprehensive Cancer Center, Ann Arbor 48109, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: van Golen
authors.forename: Z F
authors.initials: ZF
authors.lastname: Wu
authors.forename: X T
authors.initials: XT
authors.lastname: Qiao
authors.forename: L
authors.initials: L
authors.lastname: Bao
authors.forename: S D
authors.initials: SD
authors.lastname: Merajver
mesh_terms: D036002:ADP Ribose Transferases / Q000378:metabolism / Q000494:pharmacology; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001905:Botulinum Toxins; D001940:Breast / Q000166:cytology* / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002461:Cell Line, Transformed / Q000201:enzymology; D017077:Culture Media, Conditioned / Q000032:analysis / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008081:Liposomes; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics; D008561:Membrane Fusion; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000201:enzymology* / Q000235:genetics; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000201:enzymology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020741:rho GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000075024:rhoC GTP-Binding Protein
chemical_list: D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors; D015850:Interleukin-6; D016209:Interleukin-8; D008081:Liposomes; D008222:Lymphokines; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D000246:Adenosine Diphosphate Ribose; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D001905:Botulinum Toxins; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein