Back
Acta Physiologica 2012; Volume 206, Supplement 693
Joint FEPS and Spanish Physiological Society Scientific Congress 2012
9/8/2012-9/11/2012
Santiago de Compostela, Spain
STUDY OF THE ACTIONS OF AIP MUTANTS IN SOMATOTROPHS CELLS
Abstract number: P38
Garcia-Rendueles1 A. R., Diaz-Rodriguez1 E., Trivellin2 G, Garcia-Lavandeira3 M, Vila Vila4 T, Dieguez3 C, Korbonitz2 M, V Alvarez3 C
1Physiology, CIMUS-IDIS: School of Medicine and Hospital Clinico Universitario (CHUS), University of Santiago de Compostela (USC), Spain.,
2Endocrinology, Barts and the London School of Medicine, London, United Kingdom.,
3Physiology, CIMUS-IDIS: School of Medicine and Hospital Clinico Universitario (CHUS), University of Santiago de Compostela (USC), Spain.,
4Physilogy, CIMUS-IDIS: School of Medicine and Hospital Clinico Universitario (CHUS), University of Santiago de Compostela (USC), Spain.
Objectives:
Recently, germline mutations of aryl hydrocarbon receptor-interacting protein (AIP) gene located on 11q13 were identified in about 30% of all familial isolated pituitary adenoma (FIPA) families and 50% of acromegaly families (Cazabat,2007). In pituitary adenomas, bi-allelic inactivation of AIP by a combination of germline mutation and loss of heterozygosity suggest that AIP may act as a tumor suppressor gene (Vierimaa, 2006), role that is lost in the different mAIPs (Iwata, 2007). Forty-nine AIP variants have been identified to date (Chahal, 2010). In this study we want to compare the effects in proliferation and apoptosis in somatotroph cells between V49M-AIP and R16H, R304X and R304Q.
Materials:
We use the somatotroph rat pituitary cell line GH4C1 that express basal levels of AIP. The cells were transiently transfected by nucleofection. As a standard of transfection efficiency a vector expressing GFP under a CMV promoter was co-transfected. Cells were counted with a cytometer. Apoptosis was detected by Hoechst staining.
Results:
The nucleofection provided transfection efficiency over 90% in all cases. In the presence of complete medium with growth factors we observed no difference in the proliferation between the empty vector, wtAIP or any mAIPs. In deprived medium (0.1% serum) the cells transfected with the mutant V49M-AIP presented a 40% apoptosis but the rest of the mAIPs has no significant differences in apoptosis.
Conclusions:
In somatotroph cells mAIPs may not affect proliferation but V49M-AIP induces apoptosis. In cells expressing endogenous AIP this mutant seems to act as a toxic mutation. This would explain why this mutant is always in heterozygosis. The results also suggest that pro-tumoral effects of mAIP require other factors still unknown.
To cite this abstract, please use the following information:
Acta Physiologica 2012; Volume 206, Supplement 693 :P38