REDD1 is required for RAS-mediated transformation of human ovarian epithelial cells

Cell Cycle. 2009 Mar 1;8(5):780-6. doi: 10.4161/cc.8.5.7887. Epub 2009 Mar 20.


REDD1 is a gene induced by hypoxia and stimuli from multiple DNA damage. Here we show that REDD1 expression was elevated in RAS-transformed ovarian epithelial cells lines and that this overexpression increased these cells' growth rate and anchorage-independent growth on soft agar. Injection of immortalized ovarian epithelial cells overexpressing REDD1 into nude mice resulted in tumor growth that developed into papillary serous carcinoma in the peritoneal cavity. Knockdown of REDD1 expression blocked the RAS-mediated transformation of these cell lines. REDD1 overexpression decreased apoptosis and associated with increased expression of Bcl-x(L) or Bcl-2 and decreased expression of FADD, caspase1, caspase8, caspase 9, caspase 10, BAX, Bad and Bcl-X(S). Our data demonstrated that REDD1 is a key mediator in RAS-mediated transformation through an effect on anti-apoptosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Carcinoma, Papillary / etiology*
  • Carcinoma, Papillary / pathology
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic*
  • Epithelial Cells / metabolism
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Mice
  • Mice, Nude
  • Ovarian Neoplasms / etiology*
  • Ovarian Neoplasms / pathology
  • Ovary / cytology
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Small Interfering / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transplantation, Heterologous
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism
  • ras Proteins / genetics*
  • ras Proteins / metabolism


  • DDIT4 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • Transcription Factors
  • bcl-2-Associated X Protein
  • ras Proteins