title: Oncogenic potential of a C.elegans cdc25 gene is demonstrated by a gain-of-function allele.
abstract: In multicellular organisms, developmental programmes must integrate with central cell cycle regulation to co-ordinate developmental decisions with cell proliferation. Hyperplasia caused by deregulated proliferation without significant change to other aspects of developmental behaviour is a probable step towards full oncogenesis in many malignancies. CDC25 phosphatase promotes progression through the eukaryotic cell cycle by dephosphorylation of cyclin-dependent kinase and, in humans, different cdc25 family members have been implicated as potential oncogenes. Demonstrating the direct oncogenic potential of a cdc25 gene, we identify a gain-of-function mutant allele of the Caenorhabditis elegans gene cdc-25.1 that causes a deregulated proliferation of intestinal cells resulting in hyperplasia, while other aspects of intestinal cell function are retained. Using RNA-mediated interference, we demonstrate modulation of the oncogenic behaviour of this mutant, and show that a reduction of the wild-type cdc-25.1 activity can cause a failure of proliferation of intestinal and other cell types. That gain and loss of CDC-25.1 activity has opposite effects on cellular proliferation indicates its critical role in controlling C.elegans cell number.
authors.affiliation: The Wellcome Centre for Molecular Parasitology, The University of Glasgow, Anderson College, 56 Dumbarton Road, Glasgow, Scotland, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Clucas
authors.forename: Juan
authors.initials: J
authors.lastname: Cabello
authors.forename: Ingo
authors.initials: I
authors.lastname: Büssing
authors.forename: Ralf
authors.initials: R
authors.lastname: Schnabel
authors.forename: Iain L
authors.initials: IL
authors.lastname: Johnstone
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000166:cytology / Q000201:enzymology / Q000235:genetics*; D003001:Cloning, Molecular; D005799:Genes, Dominant; D018392:Genomic Imprinting; D005854:Germ Cells; D007422:Intestines / Q000166:cytology / Q000254:growth & development; D008969:Molecular Sequence Data; D009154:Mutation; D009857:Oncogenes; D020687:cdc25 Phosphatases / Q000737:chemistry / Q000235:genetics*
chemical_list: D020687:cdc25 Phosphatases