Expression of oncogenic epidermal growth factor receptor family kinases induces paclitaxel resistance and alters β-tubulin isotype expression

摘要: Oncogenic transformation confers resistance to chemotherapy through a variety of mechanisms, including suppression apoptosis, increased drug metabolism, and modification target proteins. epidermal growth factor receptor family members, EGFRvIII HER2, are expressed in broad spectrum human malignancies. Cell lines transfected with andHER2 more resistant paclitaxel-mediated cytotoxicity, tubulin polymerization induced by paclitaxel is suppressed compared cells expressing wild type receptor. Because differential expression β-tubulin isotypes has been proposed modulate resistance, we analyzed cell different oncogenes. EGFRvIII- HER2-expressing demonstrated equivalent total protein or untransfected controls. EGFRvIII-expressing increases class IVa (2.5-fold) IVb (3.1-fold) mRNA, showed (2.95-fold) mRNA. Expression oncogenic Ha-Ras did not change IV RNA levels significantly. Inhibition kinase activity using mutant allele an inactivating mutation the domain decreased 50% partially reversed paclitaxel. members associated modulation both isotype transformed This effect on may malignancies that express these