AKT inhibition is associated with chemosensitisation in the pancreatic cancer cell line MIA-PaCa-2.
AKT inhibition is associated with chemosensitisation in the pancreatic cancer cell line MIA-PaCa-2.
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DOI：
10.1038/sj.bjc.6601037
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发表时间：
2003-07-21
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
丝氨酸/苏氨酸激酶AKT的激活在胰腺癌中是常见的;其抑制使细胞对化疗的凋亡效应敏感。在AKT的各种下游靶点中，我们检测了胰腺癌细胞中NF-κB转录因子的激活和随后BCL-2基因家族的转录调控。抑制磷脂酰肌醇-3激酶或AKT导致抗凋亡基因BCL-2的蛋白水平降低和促凋亡基因BAX的蛋白水平增加。此外，抑制AKT降低了NF-κB的功能，NF-κ B能够转录调节BCL-2基因。抑制该途径对胰腺癌细胞凋亡的基础水平几乎没有影响，但增加了化疗的凋亡效应。胰腺癌细胞中AKT激活的抗凋亡作用可能涉及BCL-2蛋白的转录诱导，该蛋白赋予对凋亡的抗性;这种平衡的改变允许对化疗的凋亡作用敏感。
Activation of the serine/threonine kinase AKT is common in pancreatic cancer; inhibition of which sensitises cells to the apoptotic effect of chemotherapy. Of the various downstream targets of AKT, we examined activation of the NF-κB transcription factor and subsequent transcriptional regulation of BCL-2 gene family in pancreatic cancer cells. Inhibition of either phosphatidylinositol-3 kinase or AKT led to a decreased protein level of the antiapoptotic gene BCL-2 and an increased protein level of the proapoptotic gene BAX. Furthermore, inhibition of AKT decreased the function of NF-κB, which is capable of transcriptional regulation of the BCL-2 gene. Inhibiting this pathway had little effect on the basal level of apoptosis in pancreatic cancer cells, but increased the apoptotic effect of chemotherapy. The antiapoptotic effect of AKT activation in pancreatic cancer cells may involve transcriptional induction of a profile of BCL-2 proteins that confer resistance to apoptosis; alteration of this balance allows sensitisation to the apoptotic effect of chemotherapy.
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影响因子：
2.2
作者：
Potoka, DA;Upperman, JS;Ford, HR
通讯作者：
Ford, HR
DOI：
10.1073/pnas.95.25.14950
发表时间：
1998-12-08
影响因子：
11.1
作者：
Aoki, M;Batista, O;Vogt, PK
通讯作者：
Vogt, PK
影响因子：
2.5
作者：
Nio, Y;Dong, M;Tamura, K
通讯作者：
Tamura, K
影响因子：
4
作者：
Heinemann, V
通讯作者：
Heinemann, V
影响因子：
2.2
作者：
Perugini, RA;McDade, TP;Callery, MP
通讯作者：
Callery, MP