The annual Genes and Cancer meeting continues to attract participants from all over the world with diverse interests relating to the molecular biology of cancer. The 2006 meeting covered the broad areas of gene expression, cancer stem cells, tumour suppressors, signalling, nuclear structure and genome stability. This report describes a selection of some of the highlights of the meeting, focusing largely on unpublished data. My apologies to all those whose work could not be discussed in detail because of space constraints.
The first day started with a stimulating series of lectures, regarding the regulation of gene expression. Reuven Agami from the Netherlands Cancer Institute, Amsterdam, described a series of screens for microRNAs (miRNAs) that can regulate the expression of genes important for tumourigenesis. miRNAs are around 22 nucleotides long and act by impeding the expression of target genes. Each miRNA becomes incorporated into the RNA induced silencing complex (RISC), and the miRNA then directs RISC to the 3′ untranslated region of a mRNA, causing either degradation of the mRNA or inhibition of translation. miRNAs therefore allow cells to regulate gene expression post-translationally, and could potentially explain how the expression of particular tumour-suppressor genes is inhibited in human tumours despite the apparent absence of mutations in such genes. To screen for miRNAs that can regulate expression of the gene encoding p27, a tumour suppressor that inhibits the function of certain cyclin-dependent kinases (CDKs), a test mRNA expressing green fluorescent protein (GFP) was generated, bearing the three prime untranslated region (3′ UTR) from the p27 gene. The test mRNA was then introduced into cells together with a library expressing human miRNAs. In this way, the 221/222 cluster of miRNAs was found to reduce expression of GFP, and a similar effect was observed with an analogous mRNA expressing luciferase and also bearing the 3′ UTR of the p27 gene. The effect was shown to be specific, as it could be blocked either by point mutations in the 3′ UTR of p27, or via an ‘antagomir’ RNA molecule that blocked the function of the 221/222 miRNAs. These data raise the interesting possibility that such miRNAs may regulate the endogenous p27 gene in cells, perhaps at the translational level.
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