Oct-3/4 expression reflects tumor progression and regulates motility of bladder cancer cells

被引:140
作者
Chang, Chao-Ching [2 ]
Shieh, Gia-Shing [3 ,5 ]
Wu, Pensee [7 ]
Lin, Chia-Cheng [6 ]
Shiau, Ai-Li [2 ,3 ,4 ]
Wu, Chao-Liang [1 ,2 ,3 ]
机构
[1] Natl Cheng Kung Univ, Coll Med, Dept Biochem & Mol Biol, Tainan 70101, Taiwan
[2] Natl Cheng Kung Univ, Coll Med, Inst Basic Med Sci, Tainan 70101, Taiwan
[3] Natl Cheng Kung Univ, Coll Med, Inst Clin Med, Tainan 70101, Taiwan
[4] Natl Cheng Kung Univ, Coll Med, Dept Microbiol & Immunol, Tainan 70101, Taiwan
[5] Tainan Hosp, Dept Hlth, Dept Urol, Tainan, Taiwan
[6] Tainan Hosp, Dept Hlth, Dept Pathol, Tainan, Taiwan
[7] Univ London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, England
关键词
D O I
10.1158/0008-5472.CAN-08-0094
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Cancer and embryonic stem cells exhibit similar behavior, including immortal, undifferentiated, and invasive activities. Here, we show that in clinical samples bladder tumors with intense expression of stem cell marker Oct-3/4 (also known as POU5F1) are associated with further disease progression, greater metastasis, and shorter cancer-related survival compared with those with moderate and low expressions. Expression of Oct-3/4 is detected in human bladder transitional cell carcinoma samples and cell lines. Overexpression of Oct-3/4 enhances, whereas knockdown of Oct-3/4 expression by RNA interference reduces, migration and invasion of bladder cancer cells. Oct-3/4 can up-regulate fibroblast growth factor-4 and matrix metalloproteinase-2 (MMP-2), MMP-9, and MMP-13 production, which may contribute to tumor metastasis. Finally, we show that Ad5WS4, an E1B-55 kD-deleted adenovirus driven by the Oct-3/4 promoter, exerts potent antitumor activity against bladder cancer in a syngeneic murine tumor model. Therefore, our results implicate that Oct-3/4 may be useful as a novel tumor biological and prognostic marker and probably as a potential therapeutic target for bladder cancer.
引用
收藏
页码:6281 / 6291
页数:11
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