Correlation between differentiation and ARE binding protein tristetraprolin (TTP) in mouse epithelial mammary cells

SLOMIANSKY, V.; GATTELLI A.; KORDON E.

Bariloche, Argentina

Congreso; Gene Expression and RNA processing; 2007

International Centre for Genetic Engineering and Biotechnology (ICGEB), FCEN, UBA, IFIBYNE-CONICET, ANPCyT

Adenylate uridylate-rich elements (ARE) are identifiable sequences in the 3?UTR of mRNAs. Several authors have found ARE-binding proteins (AUBPs) that influence ARE-mRNA stability. The best characterized are AUF1, HuR, TTP, Tis11b and Tis11d. Some of these proteins increase mRNA stability (e.g. HuR) while others cause instability (e.g. AUF1, TTP). The ARE-containing genes include a number of the early response genes that regulate several physiological processes as cell proliferation or responses to the environment. Simultaneous changes in both transcription and mRNA stability have the potential to profoundly alter gene expression in a very short time. Particularly, our group has demonstrated that several mRNAs that are potential or demonstrated AUBP targets such as LIF, TNFα, thrombospondin 1 and integrin β1 are regulated during mammary gland development and involution. In addition, it has been reported that steroid hormones regulate gene expression posttranscriptionally by altering the stabilities of mRNA via the induction of some AUBPs. In order to describe the mRNA levels of some AUBPs, we performed a quantitative real time RT-PCR on different conditions both, in mammary normal glands at different development stages and in tumors induced by mouse mammary tumor virus. Results show a non-particular expression pattern of AUBPs in the tumors tested. Interestingly, we observed a significant increase of TTP mRNA levels during lactation, while there were not relevant variations of AUF-1 and HuR. In this scenario, we treated normal epithelial mammary cells HC11 with lactogenic hormones (dexamethasone, insulin and prolactin) and measured β-casein mRNA as a marker of differentiation. We found that high levels of TTP correlated with differentiation phenomena. Since it has been already demonstrated that this AUBP is a potent negative regulator of inflammatory cytokines that play an important role during mammary gland involution, we propose that TTP expression is relevant for maintaining lactation, preventing the early onset of mammary involution.