regulation of epidermal growth factor receptor signaling and erlotinib sensitivity in head and neck cancer cells by mir-7抗表皮生长因子受体信号调节和埃罗替尼mir-7敏感性在头部和颈部癌症细胞.pdfVIP

Regulation of Epidermal Growth Factor Receptor Signaling and Erlotinib Sensitivity in Head and Neck Cancer Cells by miR-7 1. 1. 1,2 1 1 Felicity C. Kalinowski , Keith M. Giles , Patrick A. Candy , Alishum Ali , Clarissa Ganda , 1 1 1,2 Michael R. Epis , Rebecca J. Webster , Peter J. Leedman * 1 Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and University of Western Australia Centre for Medical Research, Perth, Western Australia, Australia, 2 School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia Abstract Elevated expression and activity of the epidermal growth factor receptor (EGFR)/protein kinase B (Akt) signaling pathway is associated with development, progression and treatment resistance of head and neck cancer (HNC). Several studies have demonstrated that microRNA-7 (miR-7) regulates EGFR expression and Akt activity in a range of cancer cell types via its specific interaction with the EGFR mRNA 39-untranslated region (39-UTR). In the present study, we found that miR-7 regulated EGFR expression and Akt activity in HNC cell lines, and that this was associated with reduced growth in vitro and in vivo of cells (HN5) that were sensitive to the EGFR tyrosine kinase inhibitor (TKI) erlotinib (Tarceva). miR-7 acted synergistically with erlotinib to inhibit growth of erlotinib-resistant FaDu cells, an effect associated with increased inhibition of Akt activity. Microarray analysis of HN5 and FaDu cell lines transfected with miR-7 identified a common