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.

中文翻译：

---

转化生长因子β1对牛乳腺上皮细胞系MAC-T和BME-UV1程序性细胞死亡的对比作用。

以前在牛乳腺上皮细胞系BME-UV1中进行的研究表明，抑制磷脂酰肌醇-4,5-双磷酸3激酶（PI3K）/ AKT（趋同性）信号通路需要转化生长因子β1（TGFβ1）诱导的程序性细胞死亡（PCD）。为了研究这是否是TGFβ1诱导牛乳腺上皮中PCD的普遍机制，我们比较了PI3K / AKT的TGFβ1调节及其在2种牛乳腺上皮细胞系MAC-T和BME-UV1中在PCD中的作用。在MAC-T细胞中，TGFβ1促进了细胞存活，这与PI3K / AKT活性的降低（而不是增加）平行。在BME-UV1细胞中，TGFβ1诱导PCD，并伴随着对PI3K / AKT活性的时间依赖性，包括3h时AKT的磷酸化显着增加，然后在12和24小时之间减少，然后在48小时增加。抑制AKT活性增强了BME-UV1细胞中TGFβ1诱导的PCD，但对MAC-T细胞无影响，表明TGFβ1通过抑制AKT活性介导BME-UV1细胞中的PCD。抑制TGFβ1型（TβRI）激酶活性完全废除了BME-UV1细胞中TGFβ1诱导的PCD，但对TGFβ1诱导的MAC-T细胞PCD的抑制没有影响，表明TGFβ1诱导的BME-UV1细胞PCD依赖于TβRI/ SMAD信号传导。这些和先前的观察结果提示，TGFβ1对这些细胞系中PCD的不同作用可能涉及PI3K / AKT以外的非经典信号通路，并可能反映了它们的不同谱系。未来的研究应该解决这个发现，