Ectopic expression of germline genes drives malignant brain tumor growth in Drosophila

Science. 2010 Dec 24;330(6012):1824-7. doi: 10.1126/science.1195481.

Abstract

Model organisms such as the fruit fly Drosophila melanogaster can help to elucidate the molecular basis of complex diseases such as cancer. Mutations in the Drosophila gene lethal (3) malignant brain tumor cause malignant growth in the larval brain. Here we show that l(3)mbt tumors exhibited a soma-to-germline transformation through the ectopic expression of genes normally required for germline stemness, fitness, or longevity. Orthologs of some of these genes were also expressed in human somatic tumors. In addition, inactivation of any of the germline genes nanos, vasa, piwi, or aubergine suppressed l(3)mbt malignant growth. Our results demonstrate that germline traits are necessary for tumor growth in this Drosophila model and suggest that inactivation of germline genes might have tumor-suppressing effects in other species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Argonaute Proteins
  • Brain / growth & development
  • Brain / metabolism
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Cell Transformation, Neoplastic*
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster* / genetics
  • Drosophila melanogaster* / growth & development
  • Drosophila melanogaster* / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Genes, Insect*
  • Genes, Tumor Suppressor
  • Germ Cells / physiology*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Models, Animal
  • Neoplasm Transplantation
  • Peptide Initiation Factors / genetics
  • Peptide Initiation Factors / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • RNA-Induced Silencing Complex / genetics
  • RNA-Induced Silencing Complex / metabolism
  • Transplantation, Homologous
  • Up-Regulation

Substances

  • Argonaute Proteins
  • DNA-Binding Proteins
  • Drosophila Proteins
  • MicroRNAs
  • Peptide Initiation Factors
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • RNA-Induced Silencing Complex
  • aub protein, Drosophila
  • brat protein, Drosophila
  • l(3)mbt protein, Drosophila
  • piwi protein, Drosophila
  • nos protein, Drosophila
  • vas protein, Drosophila
  • DEAD-box RNA Helicases

Associated data

  • GEO/GSE24917