Abstract:
OBJECTIVES:Emerging evidence implicates the SNAIL family of transcriptional repressors in cancer development; however, the role of SNAIL in colorectal cancer has not been established. To investigate the importance of SNAIL in colorectal carcinogenesis, we examined the phenotypic and cellular consequences of SNAIL down-regulation in the MIN mouse. METHODS:Twenty-eight male MIN mice were randomized to treatment with an antisense phosphorodiamidate morpholino oligomer (AS-PMO) to SNAIL, saline, or a scrambled sequence control for 6 weeks. Tumors were scored and the molecular/cellular effects of anti-SNAIL treatment were evaluated through immunohistochemical analysis of the uninvolved intestinal mucosa for SNAIL and E-cadherin levels along with rates of apoptosis and proliferation. Furthermore, microarchitectural alterations were determined through measurement of fractal dimension. RESULTS:In the uninvolved mucosa, SNAIL AS-PMO treatment moderately decreased SNAIL protein when compared with saline-treated animals (immunohistochemistry scores 3.0 +/- 0.8 versus 2.1 +/- 0.6, respectively; P=0.01) with a concomitant increase in E-cadherin expression (1.8 +/- 0.6 versus 2.4 +/- 0.5; P < 0.05). Anti-SNAIL PMO, but not scramble control, resulted in a significant decrease in both total tumor number and incidence of tumors >2 mm (22% and 54%, respectively; P < 0.05). Furthermore, this was accompanied by an increased apoptosis rate (2-fold), decreased proliferation (3-fold), and normalization of the fractal dimension in the uninvolved intestinal mucosa. CONCLUSIONS:We show, for the first time, that SNAIL overexpression is important in intestinal tumorigenesis. While this PMO regimen afforded modest SNAIL suppression and hence tumor reduction, this provides compelling evidence for the role of SNAIL overexpression in colonic neoplasia.
journal_name
Mol Cancer Therjournal_title
Molecular cancer therapeuticsauthors
Roy HK,Iversen P,Hart J,Liu Y,Koetsier JL,Kim Y,Kunte DP,Madugula M,Backman V,Wali RKkeywords:
subject
Has Abstractpub_date
2004-09-01 00:00:00pages
1159-65issue
9eissn
1535-7163issn
1538-8514pii
3/9/1159journal_volume
3pub_type
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journal_title:Molecular cancer therapeutics
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journal_title:Molecular cancer therapeutics
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journal_title:Molecular cancer therapeutics
pub_type: 临床试验,杂志文章
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章,评审
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journal_title:Molecular cancer therapeutics
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-08-0456
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pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-06-0305
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-04-0328
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pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-11-0584
更新日期:2012-02-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-11-0855
更新日期:2012-04-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:
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doi:
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pub_type: 杂志文章
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-09-0543
更新日期:2009-12-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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更新日期:2003-08-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-12-0880
更新日期:2013-04-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-08-0562
更新日期:2008-12-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2011-05-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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更新日期:2012-06-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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