Contrasting effects of transforming growth factor β1 on programmed cell death of bovine mammary epithelial cell lines MAC-T and BME-UV1

摘要

A previous study in the bovine mammary epithelialcell line BME-UV1 demonstrated that suppression ofthe phosphatidylinositol-4,5-biphosphate 3 kinase(PI3K)/AKT (somatotropic) signaling pathway wasrequired for transforming growth factor β1 (TGFβ1)–induced programmed cell death (PCD). To investigatewhether this is a universal mechanism for TGFβ1 toinduce PCD in bovine mammary epithelium, we comparedTGFβ1 modulation of PI3K/AKT and its role inPCD in 2 bovine mammary epithelial cell lines: MAC-Tand BME-UV1. In MAC-T cells, TGFβ1 promoted cellsurvival, and this paralleled a reduction in PI3K/AKTactivity, rather than an increase. In BME-UV1 cells,TGFβ1 induced PCD, and this was accompanied by atime-dependent effect on PI3K/AKT activity, includingan initial significant increase in the phosphorylationof AKT at 3 h, followed by a reduction between 12 and24 h, and then an increase at 48 h. Inhibition of AKTactivity enhanced TGFβ1-induced PCD in BME-UV1cells but had no effect on MAC-T cells, suggesting thatTGFβ1 mediates PCD in BME-UV1 cells through suppressionof AKT activity. Inhibition of TGFβ receptortype I (TβRI) kinase activity completely abrogatedTGFβ1-induced PCD in BME-UV1 cells but had noeffect on TGFβ1-induced suppression of PCD in MACTcells, demonstrating that TGFβ1-induced PCD inBME-UV1 cells is dependent on TβRI/SMAD signaling.These and previous observations suggest that thedifferent effects of TGFβ1 on PCD in these cell linesmight involve noncanonical signaling pathways otherthan PI3K/AKT, and may reflect their different lineages.Future studies should address this finding, takinginto consideration the effect that different cultureconditions might have on cell phenotype.