Interleukin-2 (IL-2) and IL-6 regulate c-fos protooncogene expression in human pituitary adenoma explants

Paez-Pereda, Marcelo; Goldberg, Victoria; Chervin, Alberto; Carrizo, G.; Molina, A.; Andrada, J A; Sauer, Joachim; Renner, Ulrich; Stalla, Günter; Arzt, Eduardo

doi:10.1016/s0303-7207(96)03924-x

Cited by 42 publications

(35 citation statements)

References 68 publications

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“…Pituitary tumors were obtained from patients with hyperprolactinemia, acromegaly, Cushing's disease, or clinical diagnosis of nonfunctioning pituitary adenomas. Hormone production was confirmed by immunohistochemistry, and tumor samples were treated as explants, as described (23,29).…”

Section: Methodsmentioning

confidence: 99%

Involvement of bone morphogenetic protein 4 (BMP-4) in pituitary prolactinoma pathogenesis through a Smad/estrogen receptor crosstalk

Páez-Pereda

Giacomini

Refojo

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

167

162

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Section: Methodsmentioning

confidence: 99%

Involvement of bone morphogenetic protein 4 (BMP-4) in pituitary prolactinoma pathogenesis through a Smad/estrogen receptor crosstalk

Páez-Pereda

Giacomini

Refojo

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

167

162

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“…Notably, although this cytokine induced proliferation of GH3 lactosomatotroph cells, it was also shown to inhibit normal pituitary cells (Arzt et al 1993). Inhibitory or stimulatory actions of R246 Review m sapochnik and others IL-6 and pituitary senescence 58 4 : R246 Review IL-6 were observed in ACTH-, PRL-, GH-secreting and nonfunctioning adenomas, without association to the size or type of the tumor (Pereda et al 1996). Activation of different signaling pathways by IL-6/gp130 complex, as discussed previously, may explain the differences observed in IL-6 action on the anterior pituitary (Arzt 2001).…”

Section: Pathophysiological Role Of Il-6 In the Pituitarymentioning

confidence: 98%

Programmed cell senescence: role of IL-6 in the pituitary

Sapochnik

Fuertes

Arzt

2017

Journal of Molecular Endocrinology

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IL-6 is a pleiotropic cytokine with multiple pathophysiological functions. As a key factor of the senescence secretome, it can not only promote tumorigenesis and cell proliferation but also exert tumor suppressive functions, depending on the cellular context. IL-6, as do other cytokines, plays important roles in the function, growth and neuroendocrine responses of the anterior pituitary gland. The multiple actions of IL-6 on normal and adenomatous pituitary function, cell proliferation, angiogenesis and extracellular matrix remodeling indicate its importance in the regulation of the anterior pituitary. Pituitary tumors are mostly benign adenomas with low mitotic index and rarely became malignant. Premature senescence occurs in slow-growing benign tumors, like pituitary adenomas. The dual role of IL-6 in senescence and tumorigenesis is well represented in pituitary tumor development, as it has been demonstrated that effects of paracrine IL-6 may allow initial pituitary cell growth, whereas autocrine IL-6 in the same tumor triggers senescence and restrains aggressive growth and malignant transformation. IL-6 is instrumental in promotion and maintenance of the senescence program in pituitary adenomas.

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“…Furthermore, IL-6 has either inhibitory or stimulatory effects in different pituitary tumours (adrenocorticotrophin-, PRL-, GH-secreting and nonfunctioning adenomas), with no apparent association between the kind of response and tumour type or size. Using blocking antibodies it was observed that endogenous pituitary IL-6 regulates the early gene c-fos expression in adenoma explants, but not in monolayer cultures (19). This may indicate that cell -cell interactions are important for the control of c-fos expression and, hence, for the control of cell proliferation in the pituitary gland.…”

Section: Introductionmentioning

confidence: 99%

Involvement of the gp130 cytokine transducer in MtT/S pituitary somatotroph tumour development in an autocrine-paracrine model

Graciarena

Carbia-Nagashima²,

Onofri

et al. 2004

European Journal of Endocrinology

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Objective: gp130 cytokines are placed as auto-paracrine regulators of pituitary function, since they, as well as their receptors, have been shown to be expressed in and to act in normal and tumoral anterior pituitary cells. The objective of this work was to study their involvement in a model that shows the interaction between different cellular types that participate in a tumorigenic process. Design: The dependence of a pituitary somatotrophic cell line (MtT/S) on a gp130 cytokine-producing folliculostellate (FS) cell line (TtT/GF) for tumorigenesis in vivo has been described. In order to study the participation of gp130 cytokines in the auto-paracrine stimulation of MtT/S growth, we generated MtT/S gp130 sense (gp130-S) and gp130 antisense (gp130-AS) clones stably transfected with pcDNA3/gp130 sense and pcDNA3/gp130 antisense vectors respectively. Methods and results: Functional characterization studies revealed that gp130-AS clones have an inhibited gp130 signalling, and proliferation studies showed that they have an impaired response to gp130 cytokines but respond normally to other independent stimuli. When injected into nude mice, MtT/S clones respond differently depending on cell number; at high concentrations MtT/S clones alone generated tumours equivalent in size to tumours derived from MtT/S plus TtT/GF cells. At low concentrations, MtT/S sense and control clones generated tumours of smaller size than tumours derived from these same clones plus TtT/GF cells, showing a dependence on FS cells. In both cases MtT/S gp130-AS clones had impaired tumour development. Furthermore, vessel density was significantly lower in tumours derived from gp130-AS plus TtT/GF cells. Conclusions: This study underlines the importance of gp130 cytokines in proliferation and establishes its role in auto-paracrine pituitary growth regulation.European Journal of Endocrinology 151 595-604

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Interleukin-2 (IL-2) and IL-6 regulate c-fos protooncogene expression in human pituitary adenoma explants

Cited by 42 publications

References 68 publications

Involvement of bone morphogenetic protein 4 (BMP-4) in pituitary prolactinoma pathogenesis through a Smad/estrogen receptor crosstalk

Involvement of bone morphogenetic protein 4 (BMP-4) in pituitary prolactinoma pathogenesis through a Smad/estrogen receptor crosstalk

Programmed cell senescence: role of IL-6 in the pituitary

Involvement of the gp130 cytokine transducer in MtT/S pituitary somatotroph tumour development in an autocrine-paracrine model

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