In pancreatic cancer, interactions between caveolin-1 and RhoC GTPase, a key molecule in causing the IBC phenotype, regulate tumour cell motility and invasion.
We also demonstrated that overexpression of RhoC GTPase in human mammary epithelial (HME) cells nearly recapitulated the IBC phenotype with regards to invasion, motility and angiogenesis.
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.
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.
Of the 17 transcripts isolated and characterized from these experiments, overexpression of RhoC GTPase and loss of expression of a novel gene on 6q22, LIBC (lost in inflammatory breast cancer), were highly correlated (P<0.0095 and P<0.0013, respectively) with the inflammatory phenotype when a panel of archival inflammatory breast cancers was compared with noninflammatory stage III breast cancers by in situ hybridization.