Abstract
Abstract Abstract #4061 Inflammatory breast cancer (IBC) is the most lethal form of breast cancer, with a 5-year survival rate below 45%. The disease progresses rapidly, and is typically identified as stage IIIb upon diagnosis. IBC is characterized by widespread invasion of the dermal lymphatics by tumor emboli, which results in lymphatic blockage. It is this blockage that leads to edema, erythema, and the subsequent “peau d'orange” appearance of the breast, and thus the misnomer “inflammatory” breast cancer.
 Little is known about the mechanisms of IBC metastasis, and as such the treatments available to patients are limited. Our lab identified RhoC GTPase as an oncogenic driver of the IBC phenotype, as overexpression of RhoC in normal human mammary epithelial cells (HME) leads to increased motility, invasion, and secretion of angiogenic factors. Ensuing studies from our lab revealed that p38 is involved in mediating IBC metastasis and invasion, as demonstrated by the effects of p38 inhibitors on RhoC-transfected HMEs. The aim of the current project was to determine the means by which IBC utilizes p38, and elucidate the contributions of the specific p38 isoforms to IBC metastasis and invasion.
 We demonstrate, for the first time, differences in the transcriptional, translational, and post-translational regulation of specific p38 MAPK isoforms in breast cancer, differences which delineate IBC from other invasive breast cancers, and invasive breast cancer from normal mammary epithelia. Furthermore, we show evidence that this upregulation is driven by RhoC overexpression. The contribution of each isoform to metastasis and invasion was then determined using isoform-specific expression vectors and RNA interference (RNAi). The results of this study will be useful in designing new drugs and therapies specific for IBC. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4061.
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