Association between Microtubule Associated Protein -2 and the EGRF Signaling in Breast Cancer
Abstract
Microtubule associated proteins (MAP)-2 a component of the MAP family is a marker for neurons and its immuno-reactivity has been demonstrated in several neoplasms. We hypothesized that MAP-2 expression is deregulated in EGFR over-expressing 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 over-expressing cells than in non-EGFR over-expressing cells both at protein and mRNA levels. MCF-7 and MCF-10A cells were challenged with increasing doses of EGF (25-150 ng/ml) 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 ng/ml of EGF treatment. This observation suggested a possible mechanism of resistance in breast cancer patients with EGFR over-expression. We also found increasing resistance to growth inhibition by docetaxel in cells that were challenged with higher concentrations of EGFR (>50 ng/ml). 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 over-expressing the EGFR and exhibiting resistance to conventional therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2006
- Accession Number
- ADA466580
Entities
People
- Vaqar M. Adhami
Organizations
- University of Wisconsin–Milwaukee