Association Between Microtubule Associated Protein -2 and the EGRF Signaling in Breast Cancer
Annual rept. 31 Aug 2004-30 Aug 2005
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Microtubule associated proteins MAP-2 a component of the MAP family, is a marker for neurons and its immunoreactivity has been demonstrated in several neoplasms. We hypothesized that MAP-2 expression is deregulated in EGFR overexpressing breast cancers thus rendering them resistant to conventional therapy. Here we show that loss of MAP-2 expression in breast cancer cells during sustained activation of the EGFR results in resistance to chemotherapeutic drugs. We observed higher expression of MAP-2 in EGFR overexpressing cells than in non-EGFR overexpressing cells both at protein and mRNA levels. MCF-7 and MCF-10A cells were challenged with increasing doses of EGF 25-150 ngml and examined for the expression of phosphorylated EGFR. We observed that expression of MAP-2 in cell lines challenged with EGF increased with increasing doses of EGF, however, its expression was almost completely lost at concentrations 100 ngml of EGF treatment. This observation suggested a possible mechanism of resistance in breast cancer patients with EGFR overexpression. We also found increasing resistance to growth inhibition by docetaxel in cells that were challenged with higher concentrations of EGFR 50 ngml. This suggested that over expression of EGFR signaling in breast cancers could, in fact, be responsible for resistance to therapeutic agents. The loss of MAP-2 expression could have implications in treatment of breast cancers overexpressing the EGFR and exhibiting resistance to conventional therapy.
- Medicine and Medical Research