Interactions between progestins and heregulin (HRG) signaling pathways: HRG acts as mediator of progestins proliferative effects in mouse mammary adenocarcinomas

The present study addressed links between progestin and heregulin (HRG) signaling pathways in mammary tumors. An experimental model of hormonal carcinogenesis, in which the synthetic progestin medroxyprogesterone acetate (MPA) induced mammary adenocarcinomas in female Balb/c mice, was used. MPA indu...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Balañá, M.E., Lupu, R., Labriola, L., Charreau, E.H., Elizalde, P.V.
Formato:	JOUR
Materias:	Heregulin Mouse mammary tumors Progestin Type I insulin-like growth factor receptor antisense oligodeoxynucleotide gestagen medroxyprogesterone acetate messenger RNA neu differentiation factor somatomedin C somatomedin C receptor animal cell animal experiment article breast adenocarcinoma cell growth cell proliferation controlled study epithelium cell female hormonal carcinogenesis mitogenesis mouse nonhuman phenotype priority journal protein phosphorylation signal transduction Animalia
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_09509232_v18_n46_p6370_Balana
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_09509232_v18_n46_p6370_Balana
record_format	dspace
spelling	todo:paper_09509232_v18_n46_p6370_Balana2023-10-03T15:50:28Z Interactions between progestins and heregulin (HRG) signaling pathways: HRG acts as mediator of progestins proliferative effects in mouse mammary adenocarcinomas Balañá, M.E. Lupu, R. Labriola, L. Charreau, E.H. Elizalde, P.V. Heregulin Mouse mammary tumors Progestin Type I insulin-like growth factor receptor antisense oligodeoxynucleotide gestagen medroxyprogesterone acetate messenger RNA neu differentiation factor somatomedin C somatomedin C receptor animal cell animal experiment article breast adenocarcinoma cell growth cell proliferation controlled study epithelium cell female hormonal carcinogenesis mitogenesis mouse nonhuman phenotype priority journal protein phosphorylation signal transduction Animalia The present study addressed links between progestin and heregulin (HRG) signaling pathways in mammary tumors. An experimental model of hormonal carcinogenesis, in which the synthetic progestin medroxyprogesterone acetate (MPA) induced mammary adenocarcinomas in female Balb/c mice, was used. MPA induced an in vivo up-regulation of HRG mRNA expression in progestin-dependent (HD) tumor lines. Mammary tumor progression to a progestin-independent (HI) phenotype was accompanied by a high constitutive expression of HRG. The HRG message arose from the tumor epithelial cells. Primary cultures of malignant epithelial cells from a HD tumor line were used to investigate HRG involvement on cell proliferation. HRG induced a potent proliferative effect on these cells and potentiated MPA mitogenic effects. Blocking endogenous HRG synthesis by antisense oligodeoxynucleotides (ASODNs) to HRG mRNA inhibited MPA-induced cell growth, indicating that HRG acts as a mediator of MPA-induced growth. High levels of ErbB-2 and ErbB-3 expression and low ErbB-4 levels were found in HD cells. Treatment of these cells with either MPA or HRG resulted in tyrosine phosphorylation of both ErbB-2 and ErbB-3. Furthermore, both HRG and MPA proliferative effects were abolished when cells were treated with ASODNs to ErbB-2 mRNA, providing evidence for a critical role of ErbB-2 in HRG-induced growth. Finally, blocking type I insulin-like growth factor receptor (IGF-IR) expression with ASODN resulted in the complete inhibition of HRG proliferative effect, demonstrating that a functional IGF-IR is required for HRG mitogenic activity. These results provide the first evidence of interactions between progestins and HRB/ErbB signal transduction pathways in mammary cancer and the first demonstration that IGF-IR is required for HRG proliferative effects. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_09509232_v18_n46_p6370_Balana
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Heregulin Mouse mammary tumors Progestin Type I insulin-like growth factor receptor antisense oligodeoxynucleotide gestagen medroxyprogesterone acetate messenger RNA neu differentiation factor somatomedin C somatomedin C receptor animal cell animal experiment article breast adenocarcinoma cell growth cell proliferation controlled study epithelium cell female hormonal carcinogenesis mitogenesis mouse nonhuman phenotype priority journal protein phosphorylation signal transduction Animalia
spellingShingle	Heregulin Mouse mammary tumors Progestin Type I insulin-like growth factor receptor antisense oligodeoxynucleotide gestagen medroxyprogesterone acetate messenger RNA neu differentiation factor somatomedin C somatomedin C receptor animal cell animal experiment article breast adenocarcinoma cell growth cell proliferation controlled study epithelium cell female hormonal carcinogenesis mitogenesis mouse nonhuman phenotype priority journal protein phosphorylation signal transduction Animalia Balañá, M.E. Lupu, R. Labriola, L. Charreau, E.H. Elizalde, P.V. Interactions between progestins and heregulin (HRG) signaling pathways: HRG acts as mediator of progestins proliferative effects in mouse mammary adenocarcinomas
topic_facet	Heregulin Mouse mammary tumors Progestin Type I insulin-like growth factor receptor antisense oligodeoxynucleotide gestagen medroxyprogesterone acetate messenger RNA neu differentiation factor somatomedin C somatomedin C receptor animal cell animal experiment article breast adenocarcinoma cell growth cell proliferation controlled study epithelium cell female hormonal carcinogenesis mitogenesis mouse nonhuman phenotype priority journal protein phosphorylation signal transduction Animalia
description	The present study addressed links between progestin and heregulin (HRG) signaling pathways in mammary tumors. An experimental model of hormonal carcinogenesis, in which the synthetic progestin medroxyprogesterone acetate (MPA) induced mammary adenocarcinomas in female Balb/c mice, was used. MPA induced an in vivo up-regulation of HRG mRNA expression in progestin-dependent (HD) tumor lines. Mammary tumor progression to a progestin-independent (HI) phenotype was accompanied by a high constitutive expression of HRG. The HRG message arose from the tumor epithelial cells. Primary cultures of malignant epithelial cells from a HD tumor line were used to investigate HRG involvement on cell proliferation. HRG induced a potent proliferative effect on these cells and potentiated MPA mitogenic effects. Blocking endogenous HRG synthesis by antisense oligodeoxynucleotides (ASODNs) to HRG mRNA inhibited MPA-induced cell growth, indicating that HRG acts as a mediator of MPA-induced growth. High levels of ErbB-2 and ErbB-3 expression and low ErbB-4 levels were found in HD cells. Treatment of these cells with either MPA or HRG resulted in tyrosine phosphorylation of both ErbB-2 and ErbB-3. Furthermore, both HRG and MPA proliferative effects were abolished when cells were treated with ASODNs to ErbB-2 mRNA, providing evidence for a critical role of ErbB-2 in HRG-induced growth. Finally, blocking type I insulin-like growth factor receptor (IGF-IR) expression with ASODN resulted in the complete inhibition of HRG proliferative effect, demonstrating that a functional IGF-IR is required for HRG mitogenic activity. These results provide the first evidence of interactions between progestins and HRB/ErbB signal transduction pathways in mammary cancer and the first demonstration that IGF-IR is required for HRG proliferative effects.
format	JOUR
author	Balañá, M.E. Lupu, R. Labriola, L. Charreau, E.H. Elizalde, P.V.
author_facet	Balañá, M.E. Lupu, R. Labriola, L. Charreau, E.H. Elizalde, P.V.
author_sort	Balañá, M.E.
title	Interactions between progestins and heregulin (HRG) signaling pathways: HRG acts as mediator of progestins proliferative effects in mouse mammary adenocarcinomas
title_short	Interactions between progestins and heregulin (HRG) signaling pathways: HRG acts as mediator of progestins proliferative effects in mouse mammary adenocarcinomas
title_full	Interactions between progestins and heregulin (HRG) signaling pathways: HRG acts as mediator of progestins proliferative effects in mouse mammary adenocarcinomas
title_fullStr	Interactions between progestins and heregulin (HRG) signaling pathways: HRG acts as mediator of progestins proliferative effects in mouse mammary adenocarcinomas
title_full_unstemmed	Interactions between progestins and heregulin (HRG) signaling pathways: HRG acts as mediator of progestins proliferative effects in mouse mammary adenocarcinomas
title_sort	interactions between progestins and heregulin (hrg) signaling pathways: hrg acts as mediator of progestins proliferative effects in mouse mammary adenocarcinomas
url	http://hdl.handle.net/20.500.12110/paper_09509232_v18_n46_p6370_Balana
work_keys_str_mv	AT balaname interactionsbetweenprogestinsandheregulinhrgsignalingpathwayshrgactsasmediatorofprogestinsproliferativeeffectsinmousemammaryadenocarcinomas AT lupur interactionsbetweenprogestinsandheregulinhrgsignalingpathwayshrgactsasmediatorofprogestinsproliferativeeffectsinmousemammaryadenocarcinomas AT labriolal interactionsbetweenprogestinsandheregulinhrgsignalingpathwayshrgactsasmediatorofprogestinsproliferativeeffectsinmousemammaryadenocarcinomas AT charreaueh interactionsbetweenprogestinsandheregulinhrgsignalingpathwayshrgactsasmediatorofprogestinsproliferativeeffectsinmousemammaryadenocarcinomas AT elizaldepv interactionsbetweenprogestinsandheregulinhrgsignalingpathwayshrgactsasmediatorofprogestinsproliferativeeffectsinmousemammaryadenocarcinomas
_version_	1807319727898361856

Interactions between progestins and heregulin (HRG) signaling pathways: HRG acts as mediator of progestins proliferative effects in mouse mammary adenocarcinomas

Ejemplares similares