PMID- 22614881
OWN - NLM
STAT- MEDLINE
DCOM- 20121019
LR  - 20181201
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 41
IP  - 2
DP  - 2012 Aug
TI  - Association of amphiregulin with the cetuximab sensitivity of gastric cancer cell 
      lines.
PG  - 733-44
LID - 10.3892/ijo.2012.1479 [doi]
AB  - The therapeutic activity of the epidermal growth factor receptor (EGFR)-directed 
      monoclonal antibody cetuximab in gastric cancer is currently being investigated 
      in clinical studies. Reliable biomarkers for the identification of patients who 
      are likely to benefit from this treatment are not available. In this study, we 
      assessed the activity of cetuximab in five gastric cancer cell lines (AGS, AZ521, 
      Hs746T, LMSU and MKN1). The viability of two of these cell lines, AZ521 and MKN1, 
      was significantly reduced by cetuximab treatment. High expression and secretion 
      levels of the EGFR-binding ligand, amphiregulin (AREG), were associated with 
      cetuximab responsiveness. MET activation and mutations in Kirsten-Ras gene (KRAS) 
      were associated with cetuximab resistance. By introducing a hierarchy between 
      these markers, we established a model that facilitated the correct classification 
      of all five gastric cancer cell lines as cetuximab responsive or non-responsive. 
      The highest priority was allocated to activating KRAS mutations, followed by MET 
      activation and finally by the levels of secreted AREG. In order to validate these 
      results, we used three additional human gastric cancer cell lines (KATOIII, MKN28 
      and MKN45). In conclusion, we propose that our model allows the response of 
      gastric cancer cell lines to cetuximab treatment to be predicted.
FAU - Kneissl, Julia
AU  - Kneissl J
AD  - Institute of Pathology, Technische Universitat Munchen, Klinikum rechts der Isar, 
      Munich, Germany.
FAU - Keller, Simone
AU  - Keller S
FAU - Lorber, Thomas
AU  - Lorber T
FAU - Heindl, Stefan
AU  - Heindl S
FAU - Keller, Gisela
AU  - Keller G
FAU - Drexler, Ingo
AU  - Drexler I
FAU - Hapfelmeier, Alexander
AU  - Hapfelmeier A
FAU - Hofler, Heinz
AU  - Hofler H
FAU - Luber, Birgit
AU  - Luber B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120514
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (KRAS protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (MET protein, human)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - EC 3.6.5.2 (ras Proteins)
RN  - PQX0D8J21J (Cetuximab)
SB  - IM
MH  - Amphiregulin
MH  - Antibodies, Monoclonal/*pharmacology
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Agents/*pharmacology
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Cell Line, Tumor/drug effects
MH  - Cell Proliferation
MH  - Cell Survival/drug effects
MH  - Cetuximab
MH  - DNA Mutational Analysis
MH  - Drug Resistance, Neoplasm
MH  - EGF Family of Proteins
MH  - Enzyme Activation
MH  - Epidermal Growth Factor/metabolism
MH  - ErbB Receptors/metabolism
MH  - Glycoproteins/*metabolism
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/*metabolism
MH  - Mutation
MH  - Phosphorylation
MH  - Protein Processing, Post-Translational/drug effects
MH  - Proto-Oncogene Proteins/genetics
MH  - Proto-Oncogene Proteins c-met/metabolism
MH  - Proto-Oncogene Proteins p21(ras)
MH  - Stomach Neoplasms/*drug therapy
MH  - ras Proteins/genetics
EDAT- 2012/05/23 06:00
MHDA- 2012/10/20 06:00
CRDT- 2012/05/23 06:00
PHST- 2011/12/29 00:00 [received]
PHST- 2012/03/02 00:00 [accepted]
PHST- 2012/05/23 06:00 [entrez]
PHST- 2012/05/23 06:00 [pubmed]
PHST- 2012/10/20 06:00 [medline]
AID - 10.3892/ijo.2012.1479 [doi]
PST - ppublish
SO  - Int J Oncol. 2012 Aug;41(2):733-44. doi: 10.3892/ijo.2012.1479. Epub 2012 May 14.