Breast cancer patients with positive epidermal growth factor receptor (EGFR) expression have significantly worse post-relapse prognosis than patients with negative EGFR expression. Vinorelbine (NVB) is usually reserved as a salvage therapy after anthracyclines and taxanes in patients with breast cancer. To see whether EGFR expression has a predictive value in NVB-mediated effect on human breast cancer cells, we examined 50 primary breast cancer samples. Of these, 42% were found to be NVB sensitive by ATP-tumour chemosensitivity assay. Sensitivity was correlated with EGFR expression level (p = 0.001). To dynamically examine EGFR's effect on NVB sensitivity in breast cancer cells, we used the real-time cell electronic sensing system with EGFR-positive and EGFR-negative breast cancer cell lines, MCF-7 and MDA-MB-435s, respectively. MCF-7 is NVB sensitive, while MDA-MB-435 is NVB resistant. NVB-induced cytotoxicity to MCF-7 can be partly reversed with inhibitory anti-EGFR antibody. NVB up-regulated EGFR expression in MCF-7 cells, which affects ERK1/2 phosphorylation. This cellular response mechanism may cause greater input to non-lethally damaged cells. These data suggest that EGFR expression can be used as a prognostic factor for breast cancer sensitivity to NVB, which could help identify appropriate treatments for breast cancer.
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http://dx.doi.org/10.1111/j.1742-7843.2011.00759.x | DOI Listing |
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