FOXP1 regulation via the PI3K/Akt/p70S6K signaling pathway in breast cancer cells.
FOXP1 regulation via the PI3K/Akt/p70S6K signaling pathway in breast cancer cells.
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DOI：
10.3892/ol.2015.2885
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发表时间：
2015-03
期刊：
影响因子：
2.9
通讯作者：
Dogan AL
中科院分区：
文献类型：
--
作者：
Halacli SO;Dogan AL
Forkhead box P1（FOXP 1）蛋白表达缺失导致散发性和家族性乳腺癌患者预后不良，FOXP 1基因定位于染色体3 p14的肿瘤抑制基因座。尽管相关性研究表明FOXP 1在肿瘤抑制中具有作用，但需要确定FOXP 1的调节机制以确定其在乳腺癌中的功能。先前已经确定FOXP 1在乳腺癌中受雌激素调节，并且用双酚A治疗对于调节正常人乳腺上皮细胞系MCF-10 F的转化是有效的。此外，FOXO调节的FOXP 1激活抑制了他莫昔芬和Akt抑制剂VIII给药后MCF-10 F细胞的凋亡。目前的研究表明，FOXP 1的调节通过PI 3 K/Akt/p70 S6激酶（p70 S6 K）信号通路发生。在用磷脂酰肌醇3-激酶（PI 3 K）/Akt的抑制剂渥曼青霉素处理后，MCF 7和MDA-MB-231乳腺癌细胞表现出FOXP 1蛋白表达水平降低;在Akt的小干扰（si）RNA沉默中也观察到该结果。相比之下，与对照细胞裂解物相比，Akt的过表达导致MDA-MB-231细胞中FOXP 1蛋白表达水平增加。此外，用雷帕霉素（一种雷帕霉素/p70 S6 K级联的哺乳动物靶点的特异性抑制剂）处理导致MCF 7细胞中FOXP 1表达降低，但在对雷帕霉素诱导的抑制具有抗性的MDA-MB-231细胞中则没有。此外，使用siRNA沉默p70 S6 K导致FOXP 1表达显著降低。这些数据表明，FOXP 1蛋白表达在乳腺癌中受PI 3 K/Akt/p70 S6 K信号级联调节。
Loss of Forkhead box P1 (FOXP1) protein expression confers a poor prognosis in sporadic and familial breast cancer patients, and the FOXP1 gene maps to a tumor suppressor locus at chromosome 3p14. Although correlation studies have indicated that FOXP1 has a role in tumor suppression, determination of the regulatory mechanism of FOXP1 is required to establish its function in breast cancer. It has previously been identified that FOXP1 is regulated by estrogen in breast cancer and that treatment with bisphenol A is effective for regulating the transformation of the normal human breast epithelial cell line, MCF-10F. In addition, FOXO-regulated activation of FOXP1 inhibits the apoptosis of MCF-10F cells following tamoxifen and Akt inhibitor VIII administration. The present study indicates that FOXP1 regulation occurs via a PI3K/Akt/p70S6 kinase (p70S6K) signaling pathway. Following treatment with wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K)/Akt, MCF7 and MDA-MB-231 breast cancer cells demonstrated decreased FOXP1 protein expression levels; this result was also observed in the small interfering (si)RNA silencing of Akt. By contrast, overexpression of Akt resulted in increased FOXP1 protein expression levels in the MDA-MB-231 cells compared with the control cell lysates. Furthermore, treatment with rapamycin, a specific inhibitor of the mammalian target of rapamycin/p70S6K cascade, resulted in decreased FOXP1 expression in the MCF7 cells, but not in the MDA-MB-231 cells, which were resistant to rapamycin-induced inhibition. In addition, silencing of p70S6K using siRNA produced a marked decrease in FOXP1 expression. These data indicate that FOXP1 protein expression is regulated by a PI3K/Akt/p70S6K signaling cascade in breast cancer.
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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：
2.8
作者：
Banham, Alison H.;Boddy, Jane;Fox, Stephen B.
通讯作者：
Fox, Stephen B.
影响因子：
11.2
作者：
Gomez GG;Volinia S;Croce CM;Zanca C;Li M;Emnett R;Gutmann DH;Brennan CW;Furnari FB;Cavenee WK
通讯作者：
Cavenee WK
DOI：
10.1158/1078-0432.ccr-12-1141
发表时间：
2012-10-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Sangai T;Akcakanat A;Chen H;Tarco E;Wu Y;Do KA;Miller TW;Arteaga CL;Mills GB;Gonzalez-Angulo AM;Meric-Bernstam F
通讯作者：
Meric-Bernstam F
影响因子：
6.6
作者：
Matassa, Danilo Swann;Agliarulo, Ilenia;Esposito, Franca
通讯作者：
Esposito, Franca