Reduced expression of the cytokine transducer gp130 inhibits hormone secretion, cell growth, and tumor development of pituitary lactosomatotrophic GH3 cells

Two of the most potent cytokines that regulate anterior pituitary cell function are leukemia inhibitory factor and IL-6. These and others like IL-11 and ciliary neurotrophic factor are referred to as the gp130 cytokines because they share the gp130 glycoprotein as a common receptor initial signal tr...

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Detalles Bibliográficos
Autores: Perez Castro, C., Giacomini, D., Carbia Nagashima, A., Onofri, C., Graciarena, M., Kobayashi, K., Páez-Pereda, M., Renner, U., Stalla, G.K., Arzt, E.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2003
País:Argentina
Institución:Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
Repositorio:Biblioteca Digital (UBA-FCEN)
Idioma:inglés
OAI Identifier:paperaa:paper_00137227_v144_n2_p693_PerezCastro
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_00137227_v144_n2_p693_PerezCastro
Access Level:acceso abierto
Palabra clave:antisense oligodeoxynucleotide
complementary DNA
cytokine
glycoprotein gp 130
interleukin 11
interleukin 6
leukemia inhibitory factor
adenohypophysis
animal cell
article
carcinogenesis
cell function
cell growth
cell proliferation
cell strain GH3
clone
controlled study
gene expression
gene overexpression
genetic transfection
growth hormone release
hormone release
hypophysis cell
nonhuman
nude mouse
priority journal
prolactin release
prolactin synthesis
rat
signal transduction
transcription initiation
Animals
Antigens, CD
Cell Division
Cytokine Receptor gp130
Cytokines
Gene Expression Regulation, Neoplastic
Hormones
Membrane Glycoproteins
Mice
Mice, Nude
Neoplasm Transplantation
Pituitary Neoplasms
Rats
RNA, Messenger
Tumor Cells, Cultured
Descripción
Sumario:Two of the most potent cytokines that regulate anterior pituitary cell function are leukemia inhibitory factor and IL-6. These and others like IL-11 and ciliary neurotrophic factor are referred to as the gp130 cytokines because they share the gp130 glycoprotein as a common receptor initial signal transducer. We and others have shown that gp130 cytokines and their receptors are expressed and functional in normal and tumoral anterior pituitary cells. To study the role of gp130 cytokines in tumorigenic process, we generated gp130 cDNA gp130 sense and gp130 antisense (gp130-AS) transfected stable clones derived from lactosomatotroph GH3 cells. We examined hormone secretion and cell proliferation of these clones as well as their tumorigenic properties in athymic nude mice. Although gp130-AS clones, which have low gp130 levels and impaired signal transducer and activator of transcription 3 activity and suppressor of cytokine signaling-3 expression, showed reduced proliferation and hormone secretion (GH and prolactin) in response to gp130 cytokines, they had a normal response to gp130-independent stimuli. Moreover, gp130-AS clones showed a severely impaired in vivo tumor development. In contrast, the overexpressing gp130 clones (gp130 sense) showed no differences, compared with cells transfected with control vector. Thus, the present study provides new evidence supporting a link between gp130 and pituitary abnormal growth.