PMID- 15519654
OWN - NLM
STAT- MEDLINE
DCOM- 20050415
LR  - 20240513
IS  - 0168-8278 (Print)
IS  - 0168-8278 (Linking)
VI  - 41
IP  - 5
DP  - 2004 Nov
TI  - Enhanced epidermal growth factor receptor activation in human cholangiocarcinoma 
      cells.
PG  - 808-14
AB  - BACKGROUND/AIMS: Epidermal growth factor receptor (EGFR) signaling has been 
      implicated in the genesis and progression of cholangiocarcinoma. However, the 
      characteristics of EGFR signaling in cholangiocarcinoma cells have not been 
      characterized. Thus, we attempted to more fully characterize EGF/EGFR signaling 
      in human cholangiocarcinoma cells. METHODS: EGFR phosphorylation and 
      ubiquitination were evaluated using immunoblot techniques. EGFR internalization 
      was analyzed by immunofluorescent staining of EGFR or by immunoblot analysis for 
      biotinylated EGFR. Cell growth was assessed using the MTS assay. RESULTS: EGFR 
      activation was sustained following EGF stimulation in cholangiocarcinoma cells as 
      compared to hepatoma cells. This prolonged EGFR activation resulted in extended 
      p42/44 MAPK activation in cholangiocarcinoma cells. Despite ubiquitination, EGFR 
      activation-dependent internalization was defective in cholangiocarcinoma cells. 
      Cell growth was increased in cholangiocarcinoma cells following EGF stimulation 
      as compared to hepatoma cells, and this was significantly attenuated by EGFR 
      kinase inhibitors. The EGFR kinase inhibitors also significantly decreased COX-2 
      expression in cholangiocarcinoma cells, while this was not evident in hepatoma 
      cells. CONCLUSIONS: The results demonstrate that cholangiocarcinoma cells exhibit 
      sustained EGFR activation due to defective receptor internalization. As EGFR 
      kinase inhibitors effectively attenuated cellular growth, these agents may be 
      therapeutically efficacious in human cholangiocarcinoma.
FAU - Yoon, Jung-Hwan
AU  - Yoon JH
AD  - Department of Internal Medicine and Liver Research Institute, Seoul National 
      University College of Medicine, Seoul 110-744, South Korea.
FAU - Gwak, Geum-Youn
AU  - Gwak GY
FAU - Lee, Hyo-Suk
AU  - Lee HS
FAU - Bronk, Steven F
AU  - Bronk SF
FAU - Werneburg, Nathan W
AU  - Werneburg NW
FAU - Gores, Gregory J
AU  - Gores GJ
LA  - eng
GR  - DK 59427/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - J Hepatol
JT  - Journal of hepatology
JID - 8503886
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Membrane Proteins)
RN  - 0 (Quinazolines)
RN  - 0 (Tyrphostins)
RN  - 0 (Ubiquitin)
RN  - 170449-18-0 (RTKI cpd)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - S65743JHBS (Gefitinib)
SB  - IM
CIN - J Hepatol. 2004 Nov;41(5):859-61. doi: 10.1016/j.jhep.2004.09.003. PMID: 15519661
MH  - *Bile Duct Neoplasms
MH  - *Bile Ducts, Intrahepatic
MH  - Cell Line, Tumor
MH  - *Cholangiocarcinoma
MH  - Cyclooxygenase 2
MH  - Enzyme Inhibitors/pharmacology
MH  - ErbB Receptors/*metabolism
MH  - Gefitinib
MH  - Humans
MH  - Membrane Proteins
MH  - Phosphorylation
MH  - Prostaglandin-Endoperoxide Synthases/metabolism
MH  - Quinazolines/pharmacology
MH  - Signal Transduction/physiology
MH  - Tyrphostins/pharmacology
MH  - Ubiquitin/metabolism
EDAT- 2004/11/03 09:00
MHDA- 2005/04/16 09:00
CRDT- 2004/11/03 09:00
PHST- 2004/03/09 00:00 [received]
PHST- 2004/07/06 00:00 [revised]
PHST- 2004/07/14 00:00 [accepted]
PHST- 2004/11/03 09:00 [pubmed]
PHST- 2005/04/16 09:00 [medline]
PHST- 2004/11/03 09:00 [entrez]
AID - S0168-8278(04)00331-9 [pii]
AID - 10.1016/j.jhep.2004.07.016 [doi]
PST - ppublish
SO  - J Hepatol. 2004 Nov;41(5):808-14. doi: 10.1016/j.jhep.2004.07.016.