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Artículo

Interaction between FGFR-2, STAT5, and progesterone receptors in breast cancer

Cerliani, Juan PabloIcon ; Guillardoy, TomásIcon ; Giulianelli, Sebastian JesusIcon ; Vaque, José P.; Gutkind JS; Vanzulli, Silvia; Martins, Rubén; Zeitlin, Eduardo; Lamb, Caroline AnaIcon ; Lanari, Claudia Lee MalvinaIcon
Fecha de publicación: 05/2011
Editorial: American Association for Cancer Research
Revista: Cancer Research
ISSN: 0008-5472
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Bioquímica y Biología Molecular

Resumen

Fibroblast growth factor (FGF) receptor 2 (FGFR-2) polymorphisms have been associated with an increase in estrogen receptor and progesterone receptor (PR)-positive breast cancer risk; however, a clear mechanistic association between FGFR-2 and steroid hormone receptors remains elusive. In previous works, we have shown a cross talk between FGF2 and progestins in mouse mammary carcinomas. To investigate the mechanisms underlying these interactions and to validate our findings in a human setting, we have used T47D human breast cancer cells and human cancer tissue samples. We showed that medroxyprogesterone acetate (MPA) and FGF2 induced cell proliferation and activation of ERK, AKT, and STAT5 in T47D and in murine C4-HI cells. Nuclear interaction between PR, FGFR-2, and STAT5 after MPA and FGF2 treatment was also showed by confocal microscopy and immunoprecipitation. This effect was associated with increased transcription of PRE and/or GAS reporter genes, and of PR/STAT5-regulated genes and proteins. Two antiprogestins and the FGFR inhibitor PD173074, specifically blocked the effects induced by FGF2 or MPA respectively. The presence of PR/FGFR-2/ STAT5 complexes bound to the PRE probe was corroborated by using NoShift transcription and chromatin immunoprecipitation of the MYC promoter. Additionally, we showed that T47D cells stably transfected with constitutively active FGFR-2 gave rise to invasive carcinomas when transplanted into NOD/SCID mice. Nuclear colocalization between PR and FGFR-2/STAT5 was also observed in human breast cancer tissues. This study represents the first demonstration of a nuclear interaction between FGFR-2 and STAT5, as PR coactivators at the DNA progesterone responsive elements, suggesting that FGFRs are valid therapeutic targets for human breast cancer treatment. ©2011 AACR.
Palabras clave: Breast Cancer , Fgf2 , Fibroblast Growth Factor Receptors , Mammary Carcinomas , Progesterone Receptor
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/78708
DOI: https://dx.doi.org/10.1158/0008-5472.CAN-10-3074
URL: http://cancerres.aacrjournals.org/content/71/10/3720
Colecciones
Articulos(IBYME)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Citación
Cerliani, Juan Pablo; Guillardoy, Tomás; Giulianelli, Sebastian Jesus; Vaque, José P.; Gutkind JS; et al.; Interaction between FGFR-2, STAT5, and progesterone receptors in breast cancer; American Association for Cancer Research; Cancer Research; 71; 10; 5-2011; 3720-3731
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