CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
artículos
Título:
7) GH modulates hepatic epidermal growth factor signaling in the mouse
Autor/es:
GONZALEZ L; DÍAS ME; MIQUET J; SOTELO A; FERNANDEZ DC; DOMINICI FP ; BARTKE A; TURYN D
Revista:
JOURNAL OF ENDOCRINOLOGY
Editorial:
BIOSCIENTIFICA LTD
Referencias:
Año: 2010 vol. 204 p. 299 - 309
ISSN:
0022-0795
Resumen:
Epidermal growth factor (EGF) is a key regulator of cell
survival and proliferation involved in the pathogenesis and
progression of different types of cancer. The EGF receptor
(EGFR) is activated by binding of the specific ligand but also by
transactivation triggered by different growth factors including
GH. Chronically, elevatedGHlevels have been associated with
the progression of hepatocellular carcinoma. Considering EGF
and GH involvement in cell proliferation and their signaling
crosstalk, the objective of the present study was to analyze GH
modulatory effects on EGF signaling in liver. For this purpose,
GH receptor-knockout (GHR-KO) and GH-overexpressing
transgenic mice were used. EGFR content was significantly
decreased in GHR-KO mice. Consequently, EGF-induced
phosphorylation of EGFR, AKT, ERK1/2, STAT3, and
STAT5 was significantly decreased in these mice. In contrast,
EGFR content aswell as its basal tyrosine phosphorylation was
increased in transgenic mice overexpressing GH. However,
EGF stimulation caused similar levels of EGFR, AKT, and
ERK1/2 phosphorylation in normal and transgenic mice,
while EGF induction of STAT3 and STAT5 phosphorylation
was inhibited in the transgenic mice. Desensitization of
the STATs was related to decreased association of these
proteins to the EGFR and increased association between
STAT5 and the tyrosine phosphatase SH2-containing
phosphatase-2. While GHR knockout is associated with
diminished expression of the EGFR and a concomitant
decrease in EGF signaling, GH overexpression results in
EGFR overexpression with different effects depending on
the signaling pathway analyzed: AKT and ERK1/2 pathways
are induced by EGF, while STAT3 and STAT5 activation is
heterologously desensitized.