Functional analysis of the contribution of RhoA and RhoC GTPases to invasive breast carcinoma.
Although the RhoA and RhoC proteins comprise an important subset of the Rho GTPase family that have been implicated in invasive breast carcinomas, attributing specific functions to these individual members has been difficult. We have used a stable retroviral RNA interference approach to generate invasive breast carcinoma cells (SUM-159 cells) that lack either RhoA or RhoC expression. Analysis of these cells enabled us to deduce that RhoA impedes and RhoC stimulates invasion. Unexpectedly, this analysis also revealed a compensatory relationship between RhoA and RhoC at the level of both their expression and activation, and a reciprocal relationship between RhoA and Rac1 activation.
Simpson
Kaylene J
KJ
Division of Cancer Biology and Angiogenesis, Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston Massachusetts 02215, USA.
Dugan
Aisling S
AS
Mercurio
Arthur M
AM
D036002:ADP Ribose Transferases / Q000494:pharmacology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D006801:Humans; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000075024:rhoC GTP-Binding Protein
D034741:RNA, Small Interfering; D036002:ADP Ribose Transferases; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D000075024:rhoC GTP-Binding Protein