Fish oil targets PTEN to regulate NFkappaB for downregulation of anti-apoptotic genes in breast tumor growth.
Fish oil targets PTEN to regulate NFkappaB for downregulation of anti-apoptotic genes in breast tumor growth.
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DOI：
10.1007/s10549-008-0227-7
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发表时间：
2009-11
影响因子：
3.8
通讯作者：
Ghosh-Choudhury, Nandini
中科院分区：
文献类型：
--
作者：
Ghosh-Choudhury, Triparna;Mandal, Chandi C.;Woodruff, Kathleen;St Clair, Patricia;Fernandes, Gabriel;Choudhury, Goutam G.;Ghosh-Choudhury, Nandini
鱼油对乳腺肿瘤生长有益作用的分子机制在很大程度上还不确定。使用裸鼠异种移植模型，我们首次报告鱼油饮食显著增加乳腺肿瘤中PTEN蛋白的水平。此外，鱼油饮食减弱了肿瘤中PI 3激酶和Akt激酶的活性，导致NFκB活化的显著抑制。鱼油饮食也阻止了乳腺肿瘤中抗凋亡蛋白Bcl-2和Bcl-XL的表达，同时增加了caspase 3的活性。为了扩展这些发现，我们测试了DHA和EPA（鱼油中的两种活性ω-3脂肪酸）对培养的MDA MB-231细胞的功能作用。DHA和EPA处理后MDA MB-231细胞中PTEN mRNA和蛋白表达增加，NFκB B亚基p65磷酸化水平降低，与体内实验结果一致。此外，DHA和EPA降低Bcl-2和Bcl-XL的表达。DHA和EPA处理还抑制了NFκB B DNA结合活性和NFκ B依赖的Bcl-2和Bcl-XL基因转录。最后，我们发现PTEN表达显著抑制NFκ B依赖的Bcl-2和Bcl-XL基因的转录。综上所述，我们的数据揭示了一种新的信号通路，将鱼油饮食与增加的PTEN表达联系起来，从而减弱生长促进信号并增强凋亡信号，导致乳腺肿瘤消退。
The molecular mechanism for the beneficial effect of fish oil on breast tumor growth is largely undefined. Using the xenograft model in nude mice, we for the first time report that the fish oil diet significantly increased the level of PTEN protein in the breast tumors. In addition, the fish oil diet attenuated the PI 3 kinase and Akt kinase activity in the tumors leading to significant inhibition of NFκB activation. Fish oil diet also prevented the expression of anti-apoptotic proteins Bcl-2 and Bcl-XL in the breast tumors with concomitant increase in caspase 3 activity. To extend these findings we tested the functional effects of DHA and EPA, the two active ω-3 fatty acids of fish oil, on cultured MDA MB-231 cells. In agreement with our in vivo data, DHA and EPA treatment increased PTEN mRNA and protein expression and inhibited the phosphorylation of p65 subunit of NFκB in MDA MB-231 cells. Furthermore, DHA and EPA reduced expression of Bcl-2 and Bcl-XL. NFκB DNA binding activity and NFκB-dependent transcription of Bcl-2 and Bcl-XL genes were also prevented by DHA and EPA treatment. Finally, we showed that PTEN expression significantly inhibited NFκB-dependent transcription of Bcl-2 and Bcl-XL genes. Taken together, our data reveals a novel signaling pathway linking the fish oil diet to increased PTEN expression that attenuates the growth promoting signals and augments the apoptotic signals, resulting in breast tumor regression.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
4.8
作者：
Ghosh-Choudhury, Nandini;Mandal, Chandi Charan;Choudhury, Goutam Ghosh
通讯作者：
Choudhury, Goutam Ghosh
影响因子：
5.8
作者：
Chapman, NR;Europe-Finner, GN;Robson, SC
通讯作者：
Robson, SC
影响因子：
3.6
作者：
Bachman, KE;Argani, P;Park, BH
通讯作者：
Park, BH
DOI：
10.1006/bbrc.2001.5351
发表时间：
2001-08-10
影响因子：
3.1
作者：
Ghosh-Choudhury, N;Choudhury, GG;Harris, SE
通讯作者：
Harris, SE