Growth hormone (GH) signaling is desensitized in colon from transgenic mice overexpressing GH

GONZÁLEZ L; GÁNDOLA Y; MIQUET JG; DÍAZ ME; SOTELO AI; TURYN D

Córdoba

Congreso; The First South American Spring Symposium in Signal Transduction and Molecular Medicine (SISTAM); 2010

Transgenic mice overexpressing GH show increased growth of small bowel mucosa and reduced colonic apoptosis and frequently develop hepatocarcinoma at advanced ages. Livers from transgenic mice show increased expression of signaling molecules involved in cell proliferation and survival but response to GH and EGF (Epidermal Growth Factor) is diminished. The GH-IGF-1 system has important roles in intestinal homeostasis, growth and proliferation but the relevance of overexpressed GH for the development of colon cancer in mice is not clear. The objective of this study was to analyze the effects of GH excess on the expression and activation of signaling mediators involved in proliferation in colon. For this purpose, colon from GH-transgenic mice was studied. Although histological studies reveled polyps lesions in colon from transgenic mice, EGFR, Src, Akt, Erk1/2 and STAT5 expression and basal phosphorylation were found to be similar in normal and transgenic mice. However, GH-induced phosphorylation of STAT5 is diminished in the transgenic mice as well as EGF-induced phosphorylation of Akt. Desensitization of signaling pathways involved in cell proliferation and survival might be triggered in mice overexpressing GH to compensate exposure to high GH levels.