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Contrasting effects of transforming growth factor β1 on programmed cell death of bovine mammary epithelial cell lines MAC-T and BME-UV1
A previous study in the bovine mammary epithelial cell line BME-UV1 demonstrated that suppression of the phosphatidylinositol-4,5-biphosphate 3 kinase (PI3K)/AKT (somatotropic) signaling pathway was required for transforming growth factor β1 (TGFβ1)–induced programmed cell death (PCD). To investigat...
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Published in: | Journal of dairy science 2020-06, Vol.103 (6), p.5532-5549 |
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Main Authors: | , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | A previous study in the bovine mammary epithelial cell line BME-UV1 demonstrated that suppression of the phosphatidylinositol-4,5-biphosphate 3 kinase (PI3K)/AKT (somatotropic) signaling pathway was required for transforming growth factor β1 (TGFβ1)–induced programmed cell death (PCD). To investigate whether this is a universal mechanism for TGFβ1 to induce PCD in bovine mammary epithelium, we compared TGFβ1 modulation of PI3K/AKT and its role in PCD in 2 bovine mammary epithelial cell lines: MAC-T and BME-UV1. In MAC-T cells, TGFβ1 promoted cell survival, and this paralleled a reduction in PI3K/AKT activity, rather than an increase. In BME-UV1 cells, TGFβ1 induced PCD, and this was accompanied by a time-dependent effect on PI3K/AKT activity, including an initial significant increase in the phosphorylation of AKT at 3 h, followed by a reduction between 12 and 24 h, and then an increase at 48 h. Inhibition of AKT activity enhanced TGFβ1-induced PCD in BME-UV1 cells but had no effect on MAC-T cells, suggesting that TGFβ1 mediates PCD in BME-UV1 cells through suppression of AKT activity. Inhibition of TGFβ receptor type I (TβRI) kinase activity completely abrogated TGFβ1-induced PCD in BME-UV1 cells but had no effect on TGFβ1-induced suppression of PCD in MAC-T cells, demonstrating that TGFβ1-induced PCD in BME-UV1 cells is dependent on TβRI/SMAD signaling. These and previous observations suggest that the different effects of TGFβ1 on PCD in these cell lines might involve noncanonical signaling pathways other than PI3K/AKT, and may reflect their different lineages. Future studies should address this finding, taking into consideration the effect that different culture conditions might have on cell phenotype. |
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ISSN: | 0022-0302 1525-3198 |
DOI: | 10.3168/jds.2019-17460 |