PMID: 15367710Sep 16, 2004Paper

Down-regulation of SNAIL suppresses MIN mouse tumorigenesis: modulation of apoptosis, proliferation, and fractal dimension

Molecular Cancer Therapeutics
Hemant K RoyRamesh K Wali

Abstract

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. 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. 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 d...Continue Reading

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