Involvement of the gp130 cytokine transducer in MtT/S pituitary somatotroph tumour development in an autocrine-paracrine model
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 sh...
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todo:paper_08044643_v151_n5_p595_Graciarena2023-10-03T15:39:57Z Involvement of the gp130 cytokine transducer in MtT/S pituitary somatotroph tumour development in an autocrine-paracrine model Graciarena, M. Carbia-Nagashima, A. Onofri, C. Perez-Castro, C. Giacomini, D. Renner, U. Stalla, G.K. Arzt, E. cytokine DNA glycoprotein gp 130 animal cell animal experiment animal model article autocrine effect carcinogenesis cell count cell line cell proliferation controlled study disease model genetic transfection growth regulation hypophysis cell hypophysis tumor in vivo study molecular cloning mouse nonhuman nude mouse paracrine signaling priority journal protein function rat signal transduction somatic cell tumor growth Animals Antigens, CD Blood Vessels Cell Division Cell Line Cytokine Receptor gp130 Growth Hormone Membrane Glycoproteins Mice Mice, Nude Neoplasm Transplantation Paracrine Communication Pituitary Gland, Anterior Pituitary Neoplasms Rats Transfection 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. © 2004 Society of the European Journal of Endocrinology. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_08044643_v151_n5_p595_Graciarena |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
cytokine DNA glycoprotein gp 130 animal cell animal experiment animal model article autocrine effect carcinogenesis cell count cell line cell proliferation controlled study disease model genetic transfection growth regulation hypophysis cell hypophysis tumor in vivo study molecular cloning mouse nonhuman nude mouse paracrine signaling priority journal protein function rat signal transduction somatic cell tumor growth Animals Antigens, CD Blood Vessels Cell Division Cell Line Cytokine Receptor gp130 Growth Hormone Membrane Glycoproteins Mice Mice, Nude Neoplasm Transplantation Paracrine Communication Pituitary Gland, Anterior Pituitary Neoplasms Rats Transfection |
spellingShingle |
cytokine DNA glycoprotein gp 130 animal cell animal experiment animal model article autocrine effect carcinogenesis cell count cell line cell proliferation controlled study disease model genetic transfection growth regulation hypophysis cell hypophysis tumor in vivo study molecular cloning mouse nonhuman nude mouse paracrine signaling priority journal protein function rat signal transduction somatic cell tumor growth Animals Antigens, CD Blood Vessels Cell Division Cell Line Cytokine Receptor gp130 Growth Hormone Membrane Glycoproteins Mice Mice, Nude Neoplasm Transplantation Paracrine Communication Pituitary Gland, Anterior Pituitary Neoplasms Rats Transfection Graciarena, M. Carbia-Nagashima, A. Onofri, C. Perez-Castro, C. Giacomini, D. Renner, U. Stalla, G.K. Arzt, E. Involvement of the gp130 cytokine transducer in MtT/S pituitary somatotroph tumour development in an autocrine-paracrine model |
topic_facet |
cytokine DNA glycoprotein gp 130 animal cell animal experiment animal model article autocrine effect carcinogenesis cell count cell line cell proliferation controlled study disease model genetic transfection growth regulation hypophysis cell hypophysis tumor in vivo study molecular cloning mouse nonhuman nude mouse paracrine signaling priority journal protein function rat signal transduction somatic cell tumor growth Animals Antigens, CD Blood Vessels Cell Division Cell Line Cytokine Receptor gp130 Growth Hormone Membrane Glycoproteins Mice Mice, Nude Neoplasm Transplantation Paracrine Communication Pituitary Gland, Anterior Pituitary Neoplasms Rats Transfection |
description |
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. © 2004 Society of the European Journal of Endocrinology. |
format |
JOUR |
author |
Graciarena, M. Carbia-Nagashima, A. Onofri, C. Perez-Castro, C. Giacomini, D. Renner, U. Stalla, G.K. Arzt, E. |
author_facet |
Graciarena, M. Carbia-Nagashima, A. Onofri, C. Perez-Castro, C. Giacomini, D. Renner, U. Stalla, G.K. Arzt, E. |
author_sort |
Graciarena, M. |
title |
Involvement of the gp130 cytokine transducer in MtT/S pituitary somatotroph tumour development in an autocrine-paracrine model |
title_short |
Involvement of the gp130 cytokine transducer in MtT/S pituitary somatotroph tumour development in an autocrine-paracrine model |
title_full |
Involvement of the gp130 cytokine transducer in MtT/S pituitary somatotroph tumour development in an autocrine-paracrine model |
title_fullStr |
Involvement of the gp130 cytokine transducer in MtT/S pituitary somatotroph tumour development in an autocrine-paracrine model |
title_full_unstemmed |
Involvement of the gp130 cytokine transducer in MtT/S pituitary somatotroph tumour development in an autocrine-paracrine model |
title_sort |
involvement of the gp130 cytokine transducer in mtt/s pituitary somatotroph tumour development in an autocrine-paracrine model |
url |
http://hdl.handle.net/20.500.12110/paper_08044643_v151_n5_p595_Graciarena |
work_keys_str_mv |
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