Inhibition of Akt/FOXO3a signaling by constitutively active FOXO3a suppresses growth of follicular thyroid cancer cell lines

被引：15

作者：

Hong, Zhen-Yu ^{[1
,2
,3
]}

Lee, Hyeon Jung ^{[1
,2
,3
]}

Shin, Dong Yeob ^{[1
,2
,3
]}

Kim, Suk Kyoung ^{[1
,2
,3
]}

Seo, MiRan ^{[1
,2
,3
]}

Lee, Eun Jig ^{[1
,2
,3
,4
]}

机构：

[1] Yonsei Univ, Coll Med, Brain Korea Project Med Sci 21, Seoul 120752, South Korea

[2] Yonsei Univ, Coll Med, Inst Endocrine Res, Dept Endocrinol, Seoul 120752, South Korea

[3] Severance Integrat Res Inst Cerebral & Cardiovasc, Seoul, South Korea

[4] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA

来源：

CANCER LETTERS | 2012年 / 314卷 / 01期

关键词：

FOXO3a; Follicular thyroid cancer; Gene therapy; FORKHEAD TRANSCRIPTION FACTOR; FACTOR AFX; KINASE-B; APOPTOSIS; PROTEIN; AKT; EXPRESSION; GENE; PHOSPHORYLATION; DOWNSTREAM;

D O I：

10.1016/j.canlet.2011.09.010

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Akt-dependent FOXO3a cytoplasmic translocation is an important tumorigenic mechanism for escaping from apoptosis in cancer cells. In the present study, we examined whether non-phosphorylatable FOXO3a can inhibit cell growth of various follicular thyroid carcinoma (FTC) cell lines. Adenovirus carrying the FOXO3a-triple mutant (TM) sequence including point mutations at three Akt phosphorylation sites (Ad-FOXO3a-TM) was generated and transduced to the cells to mimic inhibition of Akt/FOXO3a signal. Transduction of Ad-FOXO3a-TM to FTC133 cells induced cell cycle arrest and apoptosis. Injection of Ad-FOXO3a-TM suppressed the growth of xenograft tumors in athymic mice. Consequently, our results indicate that gene therapy based on Ad-FOXO3a-TM has therapeutic potential for FTC. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

引用

页码：34 / 40

页数：7

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