Inhibition of AKT survival pathway by a small molecule inhibitor in human endometrial cancer cells

被引:65
作者
Jin, X
Gossett, DR
Wang, S
Yang, D
Cao, Y
Chen, J
Guo, R
Reynolds, RK
Lin, J [1 ]
机构
[1] Ohio State Univ, Columbus Childrens Res Inst, Ctr Childhood Canc, Columbus, OH 43205 USA
[2] Univ Michigan, Dept Pathol, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Dept Obstet & Gynecol, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA
[4] Univ Michigan, Dept Internal Med, Ctr Comprehens Canc, Div Hematol, Ann Arbor, MI 48109 USA
关键词
AKT; PTEN; endometrial cancer; apoptosis; experimental therapeutics;
D O I
10.1038/sj.bjc.6602214
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The PTEN (phosphatase and tensin homolog deleted on chromosome 10) tumour suppressor is mutated in 40-50% of human endometrial cancers. PTEN exerts its effects in part via inhibition of the antiapoptotic protein AKT. We demonstrate that two endometrial cancer cell lines that harbour PTEN mutations, Ishikawa and RL95-2, have high levels of phosphorylated AKT and high AKT kinase activity. Two additional endometrial cancer cell lines that express wild-type PTEN, HecIA and KLE, have little phosphorylated AKT and minimal demonstrable AKT kinase activity. We tested a potential inhibitor of the AKT pathway, API-59CJ-OMe, in these four cell lines. We found that API-59CJ-OMe inhibits AKT kinase activity and induces apoptosis in the Ishikawa and RL95-2 cell lines with high AKT activity, but has little effect on HecIA and KLE cells without AKT activity. API-59CJ-OMe may therefore have therapeutic potential for those endometrial cancers that harbour PTEN mutations and AKT activation.
引用
收藏
页码:1808 / 1812
页数:5
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