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Snail-regulated genes in malignant melanoma
Silke Kuphal1, Hans G Palm, Ina Poser
1Institute of Pathology, University of Regensburg, D-93053 Regensburg, Germany.
Melanoma Research
|July 22, 2005
Summary
The transcription factor Snail controls epithelial-mesenchymal transition (EMT) and melanoma progression. Inhibiting Snail (as Snail) re-induced E-cadherin and altered expression of EMT-related genes in melanoma cells.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- Epithelial-mesenchymal transition (EMT) is crucial for development and cancer progression.
- Snail, a zinc-finger transcription factor, regulates EMT and is implicated in melanoma.
- E-cadherin expression changes are key early events in melanoma progression.
Purpose of the Study:
- To investigate the role of Snail in regulating gene expression in melanoma cells.
- To compare gene expression profiles between melanoma cells and those with inhibited Snail expression.
- To determine if Snail or E-cadherin is the primary regulator of EMT-associated genes.
Main Methods:
- Utilized a human cancer cDNA array to compare gene expression in Mel Im melanoma cells versus Mel Im cells with stable antisense (as) Snail cDNA transfection.
- Validated differential gene expression at the mRNA level using quantitative real-time polymerase chain reaction (qRT-PCR).
- Assessed the regulatory influence of Snail and E-cadherin on selected genes.
Main Results:
- Inhibition of Snail (as Snail) led to the re-induction of E-cadherin expression.
- Down-regulation of genes involved in EMT, including MMP-2, EMMPRIN, SPARC, TIMP-1, t-PA, RhoA, and Notch4, was observed.
- Expression levels of integrin beta3, NM23b, and RhoB were also measured.
Conclusions:
- Snail significantly influences the expression of genes involved in EMT processes.
- The studied genes regulated by Snail play a role in EMT, similar to Snail itself.
- E-cadherin, a target gene of Snail, does not appear to regulate the expression of these selected EMT-associated genes.