Identification of protein expression alterations in gefitinib-resistant human lung adenocarcinoma: PCNT and mPR play key roles in the development of gefitinib-associated resistance

Lin, Chi-Chen, Chen, Jing-Ting, Lin, Meng-Wei, Chan, Chia-Hao, Wen, Yueh-Feng, Wu, Shin-Bei, Chung, Ting-Wen, Lyu, Kevin W., Chou, Hsiu-Chuan and Chan, Hong-Lin (2015) Identification of protein expression alterations in gefitinib-resistant human lung adenocarcinoma: PCNT and mPR play key roles in the development of gefitinib-associated resistance. Toxicology and Applied Pharmacology, 288 (3). pp. 359-373. ISSN 0041-008X

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Abstract

Gefitinib is the first-line chemotherapeutic drug for treating non-small cell lung cancer (NSCLC), which comprises nearly 85% of all lung cancer cases worldwide. However,most patients eventually develop drug resistance after 12–18 months of treatment. Hence, investigating the drug resistance mechanism and resistance-associated biomarkers is necessary. Two lung adenocarcinoma cell lines, PC9 and gefitinib-resistant PC9/Gef, were established for examining resistance mechanisms and identifying potential therapeutic targets. Two-dimensional differential gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry were used for examining global protein expression changes between PC9 and PC9/Gef. The results revealed that 164 identified proteins were associated with the formation of gefitinib resistance in PC9 cells. Additional studies using RNA interference showed that progesterone receptor membrane component 1 and pericentrin proteins have major roles in gefitinib resistance. In conclusion, the proteomic approach enabled identifying of numerous proteins involved in gefitinib resistance. The results provide useful diagnostic markers and therapeutic candidates for treating gefitinib-resistant NSCLC.

Item Type:	Article
Additional Information:	Kevin W. Lyu is a St George's exchange student at Northumbria.
Uncontrolled Keywords:	Proteomics, DIGE, Gefitinib, Resistance, Lung adenocarcinoma, mPR, PCNT
Subjects:	B200 Pharmacology, Toxicology and Pharmacy
Department:	Faculties > Health and Life Sciences > Applied Sciences
Depositing User:	Paul Burns
Date Deposited:	20 Oct 2015 10:06
Last Modified:	12 Oct 2019 18:30
URI:	http://nrl.northumbria.ac.uk/id/eprint/24045

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