PMID- 21959795
OWN - NLM
STAT- MEDLINE
DCOM- 20120719
LR  - 20220321
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 227
IP  - 7
DP  - 2012 Jul
TI  - Gefitinib resistance in HCC mahlavu cells: upregulation of CD133 expression, 
      activation of IGF-1R signaling pathway, and enhancement of IGF-1R nuclear 
      translocation.
PG  - 2947-52
LID - 10.1002/jcp.23041 [doi]
AB  - Hepatocellular carcinoma (HCC) is the major form of primary liver cancer which 
      accounts for more than half million deaths annually worldwide. While the 
      incidence of HCC is still on the rise, options of treatment are limited and the 
      overall survival rate is poor. The acquisition of cancer drug resistance remains 
      one of the key hurdles to successful treatment. Clearly, a thorough understanding 
      of the underlying mechanisms is needed for new strategies to design novel 
      treatments and/or to improve the current therapies. In the present study, we 
      examined the expression of cancer stem cell (CSC) marker CD133, the activation of 
      insulin-like growth factor 1 receptor (IGF-1R) signaling, and the nuclear 
      translocation of IGF-1R in HCC Mahlavu cells under the treatment of gefitinib, a 
      cancer drug that inhibits epidermal growth factor receptor (EGFR) pathway. Our 
      results demonstrated that Mahlavu cells exhibited strong gefitinib resistance and 
      the CD133 expression level was dramatically increased (from 3.88% to 32%) after 
      drug treatment. In addition, the gefitinib treated cells displayed increased 
      levels of phosphorylation in IGF-1R and Akt, indicating the intensified 
      activation of this cancer-associated signaling pathway. Moreover, we revealed 
      that IGF-1R underwent nuclear translocation in gefitinib treated cells using 
      confocal microscopy. The IGF-1R nuclear translocation was enhanced under 
      gefitinib treatment and appeared in a dose-dependent manner. Our findings suggest 
      that increased IGF-1R nuclear translocation after gefitinib treatment may 
      contribute to the drug resistance and IGF1-R activation, which might also 
      associate with the upregulation of CD133 expression.
CI  - Copyright (c) 2011 Wiley Periodicals, Inc.
FAU - Bodzin, Adam S
AU  - Bodzin AS
AD  - Division of Transplantation, Department of Surgery, Thomas Jefferson University, 
      Philadelphia, PA 19107, USA.
FAU - Wei, Zhengyu
AU  - Wei Z
FAU - Hurtt, Reginald
AU  - Hurtt R
FAU - Gu, Tina
AU  - Gu T
FAU - Doria, Cataldo
AU  - Doria C
LA  - eng
GR  - 5 P30 CA-56036/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (AC133 Antigen)
RN  - 0 (Antigens, CD)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Glycoproteins)
RN  - 0 (PROM1 protein, human)
RN  - 0 (Peptides)
RN  - 0 (Quinazolines)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - AC133 Antigen
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Antigens, CD/*genetics/metabolism
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Carcinoma, Hepatocellular/*drug therapy/genetics/metabolism
MH  - Cell Line, Tumor
MH  - Cell Nucleus/drug effects/genetics/*metabolism
MH  - Drug Resistance, Neoplasm
MH  - ErbB Receptors/antagonists & inhibitors/metabolism
MH  - Gefitinib
MH  - Glycoproteins/*genetics/metabolism
MH  - Humans
MH  - Liver Neoplasms/*drug therapy/genetics/metabolism
MH  - Neoplastic Stem Cells/drug effects/metabolism
MH  - Peptides/*genetics/metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Transport/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Quinazolines/*pharmacology
MH  - Receptor, IGF Type 1/genetics/*metabolism
MH  - Signal Transduction/drug effects
MH  - Up-Regulation/drug effects
EDAT- 2011/10/01 06:00
MHDA- 2012/07/20 06:00
CRDT- 2011/10/01 06:00
PHST- 2011/10/01 06:00 [entrez]
PHST- 2011/10/01 06:00 [pubmed]
PHST- 2012/07/20 06:00 [medline]
AID - 10.1002/jcp.23041 [doi]
PST - ppublish
SO  - J Cell Physiol. 2012 Jul;227(7):2947-52. doi: 10.1002/jcp.23041.