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15417786mcr120652-sup-supplementary_figure_s3_-_pdf_file_139k.pdf (135.83 kB)

Supplementary Figure S3 from Activation of the FGF2-FGFR1 Autocrine Pathway: A Novel Mechanism of Acquired Resistance to Gefitinib in NSCLC

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posted on 2023-04-03, 16:06 authored by Hideki Terai, Kenzo Soejima, Hiroyuki Yasuda, Sohei Nakayama, Junko Hamamoto, Daisuke Arai, Kota Ishioka, Keiko Ohgino, Shinnosuke Ikemura, Takashi Sato, Satoshi Yoda, Ryosuke Satomi, Katsuhiko Naoki, Tomoko Betsuyaku

Supplementary Figure S3 - PDF file 139K,The relative expression profiles of mRNA of FGFs by microarray analysis in PC9 GR, PC9 gr1 and PC9 gr3 cells normalized to mRNA extracted from PC9 na cells. None of FGFs other than FGF2 was elevated in gefitinib resistant cell lines. Each group of columns represents the result from one microarray probe

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ARTICLE ABSTRACT

Patients with non-small cell lung cancer (NSCLC) that harbors epidermal growth factor receptor (EGFR) mutations initially respond to EGFR-tyrosine kinase inhibitors (TKI) but eventually experience relapse. Acquired resistance to EGFR-TKIs is strongly associated with patient mortality. Thus, elucidation of the mechanism of acquired resistance to EGFR-TKIs is of great importance. In this study, gefitinib-resistant cell line models were established by long-term exposure to gefitinib using the gefitinib-sensitive lung cancer cell lines, PC9 and HCC827. Expression analyses indicated that both FGFR1 and FGF2 were increased in PC9 gefitinib-resistant (PC9 GR) cells as compared with PC9 naïve (PC9 na) cells. Importantly, proliferation of gefitinib-resistant cells was dependent on the FGF2 -FGFR1 pathway. Mechanistically, inhibition of either FGF2 or FGFR1 by siRNA or FGFR inhibitor (PD173074) restored gefitinib sensitivity in PC9 GR cells. These data suggest that FGF2 -FGFR1 activation through an autocrine loop is a novel mechanism of acquired resistance to EGFR-TKIs. Mol Cancer Res; 11(7); 759–67. ©2013 AACR.

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    Molecular Cancer Research

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    Keywords

    Cell SignalingProtein tyrosine kinasesDrug ResistanceNovel mechanismsReversal of drug resistanceDrug TargetsCell surface receptor drug targetsLung CancerSmall Molecule Agents

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