TRISTETRAPROLIN (TTP) PROMOTES SURVIVAL OF HC11 MAMMARY EPITHELIAL CELLS

MICAELA STEDILE; GODDIO MV; PÉREZ CUERVO L; SCHERE LEVY C.; KORDON E

Congreso; Reunión Anual SAIC; 2017

A common feature among relevant RNAs in mammary gland can- cer is the presence of sequences enriched in adenine and uracil (AREs) situated in 3 ́untranslated regions (3 ́UTR). The stability of RNAs with AREs is regulated by proteins that bind these regions, like tristetraprolin (TTP). This protein promotes degradation of mR- NAs with AREs in their 3 ́UTR such as proinflammatory cytokines and invasiveness-associated factors.We have previously reported that TTP is expressed in the mam- mary gland, reaching the highest levels during lactation. More recently, in conditional TTP-knockout mice in which expression of this protein is downregulated specifically during lactation, we found increased cell death and augmented expression of inflammatory cytokines in the secretory epithelium. We concluded that TTP expression is required for lactation maintenance. Then, to determine whether this protein is also relevant for the survival of undifferentiated mammary cells, we analyzed cell viability of HC11 clones that were stably transfected with specific TTP-shRNAs (TTP-KD cells). Using the 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethonyphenol)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, we determined that TTP-KD cells were less viable (p