The RNA destabilizing factor and tumor suppressor gene TTP is induced by prolactin in mammary cells.

GODDIO M VICTORIA; GATTELLI ALBANA; SLOMIANSKY VICTORIA; LACUNZA, EZEQUIEL; TOCCI, JOHANNA; FACCHINETTI, MARÍA MARTA; CURINO, ALEJANDRO; LAMARRE, JONATHAN; ABBA, MARTÍN C; KORDON, EDITH C

Córdoba, Argentina

Congreso; The First South American Spring Symposium in Signal Transduction and Molecular Medicine SISTAM 2010; 2010

ARE-binding proteins (AUBPs) influence stability of specific mRNAs. Tristetraprolin (TTP),anAUBP whose expression is reduced in different cancer types, down-regulates cytokinesand invasiveness-associated proteins. Breast cancer gene expression data sets showedTTP expression decrease associated to shorter survival. Then, we found that asignificantly higher number of normal and hiperplastic breast samples display TTP positiveimmuno-staining compared to invasive carcinomas. Expression pattern in mousemammary glands revealed strong TTP induction during lactation. Similarly, mammaryHC11 cell differentiation in culture elicited expression of both, endogenous TTP andluciferase under the control of mouse TTP promoter sequences. Prolactin was required totrigger these effects and transfection with a Stat5a dominant-negative mutant abolishedTTP induction. Prolactin also induced TTP in T47-D breast cancer cells, effect that wasblocked by a JAK2 pharmacological inhibitor. Therefore, TTP expression is closelyassociated to mammary differentiation, being its transcription induced by prolactintriggeredSTAT5 activation in both, human and mouse cells. We propose that this AUBPmight play a relevant role during lactation and could exert hormone-driven tumorsuppressor activities.