REDD1 is required for RAS-mediated transformation of human ovarian epithelial cells.
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.
Chang
Bin
B
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Liu
Guangzhi
G
Yang
Gong
G
Mercado-Uribe
Imelda
I
Huang
Miao
M
Liu
Jinsong
J
D000818:Animals; D017209:Apoptosis; D002291:Carcinoma, Papillary / Q000209:etiology* / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000209:etiology* / Q000473:pathology; D010053:Ovary / Q000166:cytology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014183:Transplantation, Heterologous; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
C469991:DDIT4 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein; D018631:ras Proteins