Amplification and overexpression of oncogene Mdm2 and orphan receptor gene Nr1h4 in immortal PRKDC knockout cells

Rong Ai, Ana Sandoval, David J. Chen, Sandeep Burma, Paul Labhart

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

DNA-dependent protein kinase (DNA-PK) is required for the repair of double strand DNA breaks by nonhomologous DNA end joining. The catalytic subunit of DNA-PK, PRKDC, may also be involved in repair-related or separate cell signaling pathways. To learn more about the cellular function of DNA-PK under normal physiological conditions, we identified genes that are differentially expressed between an immortalized wild-type mouse fibroblast cell line and its DNA-PK-deficient counterpart (Prkdc -/-). The proto-oncogene Mdm2 and the farnesoid X receptor gene Nr1h4 were overexpressed in the DNA-PK-deficient cell line. We show that in the DNA-PK-deficient cell line the genes for both Mdm2 and Nr1h4 are amplified to a degree that could account for most, if not all, of their increased expression. Other genes were strongly downregulated in the DNA-PK-deficient cell line, but this opposite expression pattern was not due to gene amplification in the wild-type cells. None of these genes was differentially expressed in DNA-PK-containing and DNA-PK-deficient primary mouse embryo fibroblasts. Our results suggest a model in which DNA-PK indirectly affects the cellular gene expression profile through its caretaker role and by preventing gene amplification.

Original languageEnglish (US)
Pages (from-to)91-96
Number of pages6
JournalMolecular Biology Reports
Volume31
Issue number2
DOIs
StatePublished - Jun 1 2004

Keywords

  • DNA-dependent protein kinase
  • Mdm2
  • Prkdc
  • caretaker role
  • gene amplification
  • gene expression

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'Amplification and overexpression of oncogene Mdm2 and orphan receptor gene Nr1h4 in immortal PRKDC knockout cells'. Together they form a unique fingerprint.

  • Cite this