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Abstract:

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.

Registro:

Documento: Artículo
Título:Interactions between progestins and heregulin (HRG) signaling pathways: HRG acts as mediator of progestins proliferative effects in mouse mammary adenocarcinomas
Autor:Balañá, M.E.; Lupu, R.; Labriola, L.; Charreau, E.H.; Elizalde, P.V.
Filiación:Inst. de Biol. y Med. Exp. (IBYME), Obligado 2490, Buenos Aires 1428, Argentina
Lawrence Berkeley Natl. Laboratories, University of California Berkeley, Building 934, 1 Cyclotron Road, Berkeley, CA 94710, United States
Palabras clave: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
Año:1999
Volumen:18
Número:46
Página de inicio:6370
Página de fin:6379
DOI: http://dx.doi.org/10.1038/sj.onc.1203028
Título revista:Oncogene
Título revista abreviado:Oncogene
ISSN:09509232
CODEN:ONCNE
CAS:medroxyprogesterone acetate, 71-58-9; somatomedin C, 67763-96-6
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09509232_v18_n46_p6370_Balana

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Citas:

---------- APA ----------
Balañá, M.E., Lupu, R., Labriola, L., Charreau, E.H. & Elizalde, P.V. (1999) . Interactions between progestins and heregulin (HRG) signaling pathways: HRG acts as mediator of progestins proliferative effects in mouse mammary adenocarcinomas. Oncogene, 18(46), 6370-6379.
http://dx.doi.org/10.1038/sj.onc.1203028
---------- CHICAGO ----------
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" . Oncogene 18, no. 46 (1999) : 6370-6379.
http://dx.doi.org/10.1038/sj.onc.1203028
---------- MLA ----------
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" . Oncogene, vol. 18, no. 46, 1999, pp. 6370-6379.
http://dx.doi.org/10.1038/sj.onc.1203028
---------- VANCOUVER ----------
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. Oncogene. 1999;18(46):6370-6379.
http://dx.doi.org/10.1038/sj.onc.1203028