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

VICTORIA SLOMIANSKY.; ALBANA GATTELLI.; JONATHAN LAMARRE.; EDITH C KORDON.

Bariloche, Río Negro, Argentina

Congreso; Combined Meetings: "Gene Expression and RNA Processing" (ICGEB) and "Cell Biology, Signaling and Alternative Splicing" (EURASNET); 2007

ICGEB/EURASNET

Adenylate uridylate-rich elements (ARE) are identifiable sequences in the 3’UTR of some mRNA. Several authors have found ARE-binding proteins (AUBPs) that influence the 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 exogenous agents. Simultaneous changes in both transcription and mRNA stability have the potential to profoundly alter gene expression in a very short time. Particularly during mammary gland development, several mRNA such as LIF, TNFa, IL 11, thrombospondin 1 and integrin b1 show low levels at lactation. 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 developmental 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 in the lactation, while there are not relevant variations of AUF-1 and HuR. Previous works demonstrated that the TTP promoter present a consensus glucocorticoids response element. In this scenario, we differentiated normal epithelial mammary cells HC11 and measured b-casein mRNA as a marker of differentiation. We found that high levels of TTP correlated with differentiation phenomena. In this context, we postulate TTP as a possible candidate that could be involved in the destabilization of some mRNA that have to be diminished in differentiated cells.