PMID- 12356750
OWN - NLM
STAT- MEDLINE
DCOM- 20030212
LR  - 20210206
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 51
DP  - 2002 Dec 20
TI  - Inhibition of apoptosis by amphiregulin via an insulin-like growth factor-1 
      receptor-dependent pathway in non-small cell lung cancer cell lines.
PG  - 49127-33
AB  - Several abnormalities in the insulin-like growth factor-1 (IGF1) and erbB 
      receptors pathways stimulate the growth and survival of lung cancer cells, but 
      their mechanisms of action and cooperation are poorly understood. In this report, 
      we have identified a new mechanism of apoptosis inhibition by amphiregulin 
      through an IGF1-dependent survival pathway in non-small cell lung cancer (NSCLC) 
      cells: amphiregulin activates the IGF1 receptor that in turn induces the 
      secretion of amphiregulin and IGF1. In the absence of serum, the NSCLC cell line 
      H358 resists apoptosis and secretes factors protecting the NSCLC cell line H322 
      from serum deprivation apoptosis. IGF1 receptor inhibitor AG1024 as well as 
      epidermal growth factor receptor inhibitors AG556 and ZD1839 restore apoptosis in 
      H322 cells cultured in H358-conditioned medium. Accordingly, the anti-apoptotic 
      activity of H358-conditioned medium is completely abolished after incubation with 
      anti-amphiregulin neutralizing antibody and only partially with anti-IGF1 
      neutralizing antibody. H358-conditioned medium and amphiregulin induce IGF1 
      receptor phosphorylation in H322 cells, which is prevented by anti-amphiregulin 
      neutralizing antibody but not by AG556 or ZD1839. H358 cells secrete a high level 
      of amphiregulin that, in combination with IGF1, prevents serum deprivation 
      apoptosis. Finally, IGF1 receptor inhibitor blocks amphiregulin and IGF1 release 
      by H358 cells.
FAU - Hurbin, Amandine
AU  - Hurbin A
AD  - Groupe de Recherche sur le Cancer du Poumon, INSERM-EMI 9924, Institut Albert 
      Bonniot, La Tronche 38706 Cedex, France.
FAU - Dubrez, Laurence
AU  - Dubrez L
FAU - Coll, Jean-Luc
AU  - Coll JL
FAU - Favrot, Marie-Christine
AU  - Favrot MC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20020927
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Quinazolines)
RN  - 0 (Tyrphostins)
RN  - 0 (tyrphostin AG 1024)
RN  - 149092-35-3 (AG 556)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - Amphiregulin
MH  - Antineoplastic Agents/pharmacology
MH  - *Apoptosis
MH  - Carcinoma, Non-Small-Cell Lung/*pathology
MH  - Culture Media, Conditioned/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - EGF Family of Proteins
MH  - Gefitinib
MH  - Glycoproteins/*metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/*metabolism
MH  - Jurkat Cells
MH  - Kinetics
MH  - Lung Neoplasms/*pathology
MH  - Phosphorylation
MH  - Precipitin Tests
MH  - Quinazolines/pharmacology
MH  - Receptor Protein-Tyrosine Kinases/antagonists & inhibitors
MH  - Receptor, IGF Type 1/*metabolism
MH  - Time Factors
MH  - Tumor Cells, Cultured
MH  - Tyrosine/metabolism
MH  - Tyrphostins/pharmacology
EDAT- 2002/10/03 04:00
MHDA- 2003/02/14 04:00
CRDT- 2002/10/03 04:00
PHST- 2002/10/03 04:00 [pubmed]
PHST- 2003/02/14 04:00 [medline]
PHST- 2002/10/03 04:00 [entrez]
AID - S0021-9258(19)32874-1 [pii]
AID - 10.1074/jbc.M207584200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 Dec 20;277(51):49127-33. doi: 10.1074/jbc.M207584200. Epub 2002 
      Sep 27.