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Reduced Expression of the Cytokine Transducer gp130 Inhibits Hormone Secretion, Cell Growth, and Tumor Development of Pituitary Lactosomatotrophic GH3 Cells

Departamento de Fisiología y Biología Molecular y Celular (C.P.C., D.G., A.C.N., M.G., K.K., E.A.), Laboratorio de Fisiología y Biología Molecular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EHA Buenos Aires, Argentina; and Department of Endocrinology (C.O., M.P.-P., U.R., G.K.S.), Max Planck Institute of Psychiatry, 80804 Munich, Germany

Address all correspondence and requests for reprints to: Dr. E. Arzt, Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología y Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II, C1428EHA, Buenos Aires, Argentina. E-mail: earzt{at}fbmc.fcen.uba.ar.

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.

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