PMID- 15856020
OWN - NLM
STAT- MEDLINE
DCOM- 20050728
LR  - 20211203
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 24
IP  - 28
DP  - 2005 Jun 30
TI  - Involvement of EGF receptor and c-Src in the survival signals induced by 
      TGF-beta1 in hepatocytes.
PG  - 4580-7
AB  - Transforming growth factor beta1 (TGF-beta1) belongs to a family of polypeptide 
      factors, whose cytostatic and apoptotic functions help restrain the growth of 
      mammalian cells. Although solid data established the role of TGF-beta's as 
      suppressor factors in tumorigenic processes, in the context of an advanced stage 
      of disease, TGF-beta's could also play a pro-oncogenic role. We have previously 
      shown that TGF-beta1 induces both pro- and anti-apoptotic signals in foetal rat 
      hepatocytes. In this work, we have focused on its anti-apoptotic mechanism. We 
      show that TGF-beta1 activates the epidermal growth factor receptor (EGFR) and 
      phosphorylates c-Src. EGFR is required for Akt activation. Blocking EGFR 
      signalling amplifies the apoptotic response to TGF-beta1. TGF-beta1 induced a 
      rapid activation of the tumour necrosis factor-alpha-converting enzyme (TACE/ADAM 
      (a disintegrin and metalloprotease) 17). Inhibitors of TACE considerably 
      attenuated Akt activation, which suggests that TGF-beta1 activates EGF signalling 
      in hepatocytes by promoting shedding of EGF-like ligands. The activation of c-Src 
      by TGF-beta1 is EGFR dependent and is required for full Akt phosphorylation and 
      cell survival. Inhibition of EGFR does not block the epithelial-mesenchymal 
      transition (EMT) induced by TGF-beta1 in hepatocytes, which indicates that 
      activation of EGFR plays an essential role in impairing apoptosis, but it is 
      dispensable for the EMT process.
FAU - Murillo, Miguel M
AU  - Murillo MM
AD  - Departamento de Bioquimica y Biologia Molecular, Facultad de Farmacia, 
      Universidad Complutense de Madrid, Madrid 28040, Spain.
FAU - del Castillo, Gaelle
AU  - del Castillo G
FAU - Sanchez, Aranzazu
AU  - Sanchez A
FAU - Fernandez, Margarita
AU  - Fernandez M
FAU - Fabregat, Isabel
AU  - Fabregat I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Isoenzymes)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Tgfb1 protein, rat)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.1.137 (Class Ib Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.1.137 (Pik3cg protein, rat)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins pp60(c-src))
RN  - EC 2.7.11.1 (Akt1 protein, rat)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.86 (ADAM17 Protein)
RN  - EC 3.4.24.86 (Adam17 protein, rat)
SB  - IM
MH  - ADAM Proteins
MH  - ADAM17 Protein
MH  - Animals
MH  - Apoptosis/drug effects/physiology
MH  - Caspase 3
MH  - Caspases/metabolism
MH  - Cell Survival/drug effects/physiology
MH  - Cells, Cultured
MH  - Class Ib Phosphatidylinositol 3-Kinase
MH  - Epithelial Cells/metabolism
MH  - ErbB Receptors/*metabolism
MH  - Hepatocytes/*cytology/drug effects/*metabolism
MH  - Isoenzymes/metabolism
MH  - Liver/cytology/embryology
MH  - Mesoderm/metabolism
MH  - Metalloendopeptidases/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Proto-Oncogene Proteins pp60(c-src)/drug effects/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Signal Transduction
MH  - Transforming Growth Factor beta/*metabolism/pharmacology
MH  - Transforming Growth Factor beta1
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2005/04/28 09:00
MHDA- 2005/07/29 09:00
CRDT- 2005/04/28 09:00
PHST- 2005/04/28 09:00 [pubmed]
PHST- 2005/07/29 09:00 [medline]
PHST- 2005/04/28 09:00 [entrez]
AID - 1208664 [pii]
AID - 10.1038/sj.onc.1208664 [doi]
PST - ppublish
SO  - Oncogene. 2005 Jun 30;24(28):4580-7. doi: 10.1038/sj.onc.1208664.