The RNA-destabilizing factor tristetraprolin (TTP), which behaves as a tumor suppressor gene, is induced by prolactin in normal and neoplastic mammary cells

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

Los Cocos, Córdoba

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

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 shorter survival. 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.