PMID- 21168239
OWN - NLM
STAT- MEDLINE
DCOM- 20111121
LR  - 20221207
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 73
IP  - 2
DP  - 2011 Aug
TI  - Clinical and molecular evidences of epithelial to mesenchymal transition in 
      acquired resistance to EGFR-TKIs.
PG  - 176-82
LID - 10.1016/j.lungcan.2010.11.011 [doi]
AB  - BACKGROUND: Epithelial-to-mesenchymal transition (EMT), which was related with an 
      acquired resistance to gefitinib, was found in the A549 lung cancer cell line. 
      However, the clinical feasibility of this finding is still questionable. Here, we 
      investigated whether EMT could be detected in a more clinically suitable 
      situation using patient's tumor and cells with deletion mutation on exon 19 of 
      EGFR gene. METHODS: HCC827 cell line was used to establish the subline resistant 
      to EGFR-TKIs. The induction of EMT was analyzed by immunostainings and Western 
      blots in resistant cells and biopsied tissue from a patient with acquired 
      resistance to erlotinib. Migration and invasion assay was performed to 
      characterize the resistant cells. EMT-related genes expression was evaluated by 
      cDNA microarray. Phospho-receptor tyrosine kinase array analysis was carried out 
      to find bypass activating signals such as MET. RESULTS: We found that EMT 
      developed in a lung cancer patient who had an acquired resistance to erlotinib 
      while there were no known resistant mechanisms such as T790M and MET 
      amplification. CL-387,785-resistant cells (HCC827/CLR) were obtained by long-term 
      exposure to increasing concentrations of CL-387,785 (an irreversible EGFR-TKI). 
      The morphological and molecular maker changes compatible with EMT were also found 
      in HCC827/CLR cells. However, there were also no secondary T790M mutation and MET 
      amplification. Furthermore, the activity of most of tested RTKs including 
      receptor HER family was decreased suggesting that there was no bypass activating 
      signal leading to resistance. These cells showed an enhanced capability for 
      migration ( approximately 1.6-fold) and invasion ( approximately 2.8-fold). CONCLUSION: EMT should be 
      considered as one of possible mechanisms for the acquired resistance to EGFR-TKIs 
      in lung cancer cells.
CI  - Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.
FAU - Chung, Jin-Haeng
AU  - Chung JH
AD  - Department of Pathology, Seoul National University Bundang Hospital, Seoul 
      National University College of Medicine, Gyeonggi-do, Republic of Korea.
FAU - Rho, Jin Kyung
AU  - Rho JK
FAU - Xu, Xianhua
AU  - Xu X
FAU - Lee, Jong Seok
AU  - Lee JS
FAU - Yoon, Ho Il
AU  - Yoon HI
FAU - Lee, Choon Taek
AU  - Lee CT
FAU - Choi, Yun Jung
AU  - Choi YJ
FAU - Kim, Hye-Ryoun
AU  - Kim HR
FAU - Kim, Cheol Hyeon
AU  - Kim CH
FAU - Lee, Jae Cheol
AU  - Lee JC
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101217
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Quinazolines)
RN  - 0W860991D6 (Deoxycytidine)
RN  - B4W27J1Z8B (CL 387785)
RN  - BG3F62OND5 (Carboplatin)
RN  - DA87705X9K (Erlotinib Hydrochloride)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - S65743JHBS (Gefitinib)
RN  - 0 (Gemcitabine)
SB  - IM
MH  - Antineoplastic Agents/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Biomarkers, Tumor/metabolism
MH  - Carboplatin/administration & dosage
MH  - Carcinoma, Acinar Cell/diagnosis/drug therapy/secondary/surgery
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cell Shape/drug effects
MH  - Deoxycytidine/administration & dosage/analogs & derivatives
MH  - *Drug Resistance, Neoplasm
MH  - *Epithelial-Mesenchymal Transition
MH  - ErbB Receptors/*antagonists & inhibitors/genetics
MH  - Erlotinib Hydrochloride
MH  - Female
MH  - Gefitinib
MH  - Gene Expression Profiling
MH  - Humans
MH  - Lung Neoplasms/diagnosis/drug therapy/pathology/surgery
MH  - Middle Aged
MH  - Neoplasm Invasiveness
MH  - Pancreatic Neoplasms/drug therapy/pathology/secondary
MH  - Quinazolines/*pharmacology/*therapeutic use
MH  - Sequence Deletion
MH  - Gemcitabine
EDAT- 2010/12/21 06:00
MHDA- 2011/12/13 00:00
CRDT- 2010/12/21 06:00
PHST- 2010/05/26 00:00 [received]
PHST- 2010/11/22 00:00 [revised]
PHST- 2010/11/23 00:00 [accepted]
PHST- 2010/12/21 06:00 [entrez]
PHST- 2010/12/21 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
AID - S0169-5002(10)00546-5 [pii]
AID - 10.1016/j.lungcan.2010.11.011 [doi]
PST - ppublish
SO  - Lung Cancer. 2011 Aug;73(2):176-82. doi: 10.1016/j.lungcan.2010.11.011. Epub 2010 
      Dec 17.