IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Expression and regulation of tristetraprolin, an AUBP with tumor suppressor activities, in mammary cells.
Autor/es:
GODDIO, MARÍA VICTORIA; GATTELLI, ALBANA; SLOMIANSKY, VICTORIA; LACUNZA, EZEQUIEL; TOCCI, JOHANNA MELISA; FACCHINETTI, MARÍA MARTA; CURINO, ALEJANDRO; LAMARRE, JONATHAN; ABBA, MARTÍN C.; KORDON, EDITH C
Lugar:
Los Cocos, Córdoba
Reunión:
Simposio; Symposium in Signal Transduction and Molecular Medicine; 2010
Resumen:
ARE-binding proteins (AUBPs) influence stability of specific mRNAs. Tristetraprolin (TTP), an AUBP whose expression is reduced in different cancer types, down-regulates cytokines and invasiveness-associated proteins. Breast cancer gene expression data sets showed TTP expression decrease associated to poor prognosis marker. Then, we found that a significantly higher number of normal and hiperplastic breast samples display TTP positive immuno-staining compared to invasive carcinomas. Expression pattern in mouse mammary glands revealed strong TTP induction during lactation. Similarly, mammary HC11 cell differentiation in culture elicited expression of both, endogenous TTP and luciferase under the control of mouse TTP promoter sequences. Prolactin was required to trigger these effects and transfection with a Stat5a dominant-negative mutant abolished TTP induction. Prolactin also induced TTP in T47-D breast cancer cells, effect that was blocked by a JAK2 pharmacological inhibitor. Therefore, TTP expression is closely associated to mammary differentiation, being its transcription induced by prolactin-triggered STAT5 activation in both, human and mouse cells. We propose that this AUBP might play a relevant role during lactation and could exert hormone-driven tumor suppressor activities.