Abstract:
BACKGROUND:Renal cell carcinoma (RCC) is highly resistant to chemotherapy because of a high apoptotic threshold. Recent evidences suggest that GSK-3beta positively regulates human pancreatic cancer and leukaemia cell survival in part through regulation of nuclear factor (NF-kappaB)-mediated expression of anti-apoptotic molecules. Our objectives were to determine the expression pattern of GSK-3beta and to assess the anti-cancer effect of GSK-3beta inhibition in RCC. METHODS:Immunohistochemistry and nuclear/cytosolic fractionation were performed to determine the expression pattern of GSK-3beta in human RCCs. We used small molecule inhibitor, RNA interference, western blotting, quantitative RT-PCR, BrDU incorporation and MTS assays to study the effect of GSK-3beta inactivation on renal cancer cell proliferation and survival. RESULTS:We detected aberrant nuclear accumulation of GSK-3beta in RCC cell lines and in 68 out of 74 (91.89%) human RCCs. We found that pharmacological inhibition of GSK-3 led to a decrease in proliferation and survival of renal cancer cells. We observed that inhibition of GSK-3 results in decreased expression of NF-kappaB target genes Bcl-2 and XIAP and a subsequent increase in renal cancer cell apoptosis. Moreover, we show that GSK-3 inhibitor and Docetaxel synergistically suppress proliferation and survival of renal cancer cells. CONCLUSIONS:Our results show nuclear accumulation of GSK-3beta as a new marker of human RCC, identify that GSK-3 positively regulates RCC cell survival and proliferation and suggest inhibition of GSK-3 as a new promising approach in the treatment of human renal cancer.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Bilim V,Ougolkov A,Yuuki K,Naito S,Kawazoe H,Muto A,Oya M,Billadeau D,Motoyama T,Tomita Ydoi
10.1038/sj.bjc.6605437subject
Has Abstractpub_date
2009-12-15 00:00:00pages
2005-14issue
12eissn
0007-0920issn
1532-1827pii
6605437journal_volume
101pub_type
杂志文章abstract::The incidence of B cell leukaemia in 186 consecutive untreated patients with histologically defined B cell neoplasms is described. The lymphomas were classified by the Kiel convention. B cell leukaemia in the context of this paper refers to the situation where a neoplastic clone of B cells in the blood greatly outnumb...
journal_title:British journal of cancer
pub_type: 杂志文章
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更新日期:1983-08-01 00:00:00
abstract:BACKGROUND:Colorectal cancer (CRC) diagnoses and disease-specific survival (DSS) vary between ethnic groups in the United States. However, few studies have assessed differences among Asian subgroups. METHODS:The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients with invasive CRC...
journal_title:British journal of cancer
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journal_title:British journal of cancer
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更新日期:1989-11-01 00:00:00
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pub_type: 杂志文章
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pub_type: 共识发展会议,杂志文章,评审
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更新日期:2003-06-02 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
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doi:10.1054/bjoc.1999.0918
更新日期:2000-01-01 00:00:00
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journal_title:British journal of cancer
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更新日期:2011-12-06 00:00:00
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journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
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更新日期:1995-07-01 00:00:00
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pub_type: 临床试验,杂志文章,多中心研究
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journal_title:British journal of cancer
pub_type: 杂志文章
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更新日期:1976-08-01 00:00:00
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pub_type: 临床试验,杂志文章
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journal_title:British journal of cancer
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doi:10.1038/sj.bjc.6602981
更新日期:2006-03-13 00:00:00
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pub_type: 杂志文章
doi:10.1038/sj.bjc.6690365
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更新日期:2005-11-14 00:00:00
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pub_type: 杂志文章
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更新日期:2010-07-27 00:00:00
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pub_type: 杂志文章
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更新日期:2007-09-17 00:00:00
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pub_type: 杂志文章
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更新日期:2020-07-01 00:00:00
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journal_title:British journal of cancer
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