Elevated BCRP/ABCG2 Expression Confers Acquired Resistance to Gefitinib in Wild-Type EGFR-Expressing Cells

Yun Ju Chen, Wei Chien Huang, Ya Ling Wei, Sheng Chieh Hsu, Ping Yuan, Heather Y. Lin, Ignacio I. Wistuba, J. Jack Lee, Chia Jui Yen, Wu Chou Su, Kwang Yu Chang, Wen Chang Chang, Tse Chuan Chou, Chao Kai Chou, Chang Hai Tsai, Mien Chie Hung

Research output: Contribution to journalArticle

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Abstract

Background: The sensitivity of non-small cell lung cancer (NSCLC) patients to EGFR tyrosine kinase inhibitors (TKIs) is strongly associated with activating EGFR mutations. Although not as sensitive as patients harboring these mutations, some patients with wild-type EGFR (wtEGFR) remain responsive to EGFR TKIs, suggesting that the existence of unexplored mechanisms renders most of wtEGFR-expressing cancer cells insensitive. Methodology/Principal Findings: Here, we show that acquired resistance of wtEGFR-expressing cancer cells to an EGFR TKI, gefitinib, is associated with elevated expression of breast cancer resistance protein (BCRP/ABCG2), which in turn leads to gefitinib efflux from cells. In addition, BCRP/ABCG2 expression correlates with poor response to gefitinib in both cancer cell lines and lung cancer patients with wtEGFR. Co-treatment with BCRP/ABCG2 inhibitors enhanced the anti-tumor activity of gefitinib. Conclusions/Significance: Thus, BCRP/ABCG2 expression may be a predictor for poor efficacy of gefitinib treatment, and targeting BCRP/ABCG2 may broaden the use of gefitinib in patients with wtEGFR.

Original languageEnglish
Article numbere21428
JournalPLoS One
Volume6
Issue number6
DOIs
Publication statusPublished - 2011
Externally publishedYes

Fingerprint

tyrosine
Cells
phosphotransferases (kinases)
Protein-Tyrosine Kinases
lung neoplasms
cells
Neoplasms
mutation
Mutation
breast neoplasms
Non-Small Cell Lung Carcinoma
cell lines
gefitinib
Tumors
Lung Neoplasms
neoplasms
Breast Neoplasms
Cell Line
neoplasm cells
proteins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Chen, Y. J., Huang, W. C., Wei, Y. L., Hsu, S. C., Yuan, P., Lin, H. Y., ... Hung, M. C. (2011). Elevated BCRP/ABCG2 Expression Confers Acquired Resistance to Gefitinib in Wild-Type EGFR-Expressing Cells. PLoS One, 6(6), [e21428]. https://doi.org/10.1371/journal.pone.0021428

Elevated BCRP/ABCG2 Expression Confers Acquired Resistance to Gefitinib in Wild-Type EGFR-Expressing Cells. / Chen, Yun Ju; Huang, Wei Chien; Wei, Ya Ling; Hsu, Sheng Chieh; Yuan, Ping; Lin, Heather Y.; Wistuba, Ignacio I.; Lee, J. Jack; Yen, Chia Jui; Su, Wu Chou; Chang, Kwang Yu; Chang, Wen Chang; Chou, Tse Chuan; Chou, Chao Kai; Tsai, Chang Hai; Hung, Mien Chie.

In: PLoS One, Vol. 6, No. 6, e21428, 2011.

Research output: Contribution to journalArticle

Chen, YJ, Huang, WC, Wei, YL, Hsu, SC, Yuan, P, Lin, HY, Wistuba, II, Lee, JJ, Yen, CJ, Su, WC, Chang, KY, Chang, WC, Chou, TC, Chou, CK, Tsai, CH & Hung, MC 2011, 'Elevated BCRP/ABCG2 Expression Confers Acquired Resistance to Gefitinib in Wild-Type EGFR-Expressing Cells', PLoS One, vol. 6, no. 6, e21428. https://doi.org/10.1371/journal.pone.0021428
Chen, Yun Ju ; Huang, Wei Chien ; Wei, Ya Ling ; Hsu, Sheng Chieh ; Yuan, Ping ; Lin, Heather Y. ; Wistuba, Ignacio I. ; Lee, J. Jack ; Yen, Chia Jui ; Su, Wu Chou ; Chang, Kwang Yu ; Chang, Wen Chang ; Chou, Tse Chuan ; Chou, Chao Kai ; Tsai, Chang Hai ; Hung, Mien Chie. / Elevated BCRP/ABCG2 Expression Confers Acquired Resistance to Gefitinib in Wild-Type EGFR-Expressing Cells. In: PLoS One. 2011 ; Vol. 6, No. 6.
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AU - Wei, Ya Ling

AU - Hsu, Sheng Chieh

AU - Yuan, Ping

AU - Lin, Heather Y.

AU - Wistuba, Ignacio I.

AU - Lee, J. Jack

AU - Yen, Chia Jui

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AU - Chang, Kwang Yu

AU - Chang, Wen Chang

AU - Chou, Tse Chuan

AU - Chou, Chao Kai

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AU - Hung, Mien Chie

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