期刊
DNA REPAIR
卷 7, 期 2, 页码 177-186出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.dnarep.2007.09.008
关键词
base excision repair; apurinic endocuclease1/redox; effector factor-1; tumor xenograft; ovarian cancer; cell cycle
资金
- NCI NIH HHS [R01 CA106298-04, R21 CA122298, R01 CA114571, CA 122298, R01 CA094025, R21 CA122298-01A1, CA 106298, R01 CA114571-02, R01 CA094025-05, CA 114574, CA 094025, R01 CA114574, R01 CA106298] Funding Source: Medline
Apurinic endonuclease 1/redox effector factor-1 (Ape1/Ref-1 or Ape1) is an essential protein with two distinct functions. It is a DNA repair enzyme in the base excision repair (BER) pathway and a reduction-oxidation (redox) signaling factor maintaining transcription factors in an active reduced state. Our laboratory previously demonstrated that Ape1 is overexpressed in ovarian cancer and potentially contributes to resistance. Therefore, we utilized siRNA technology to knockdown protein levels of Ape1 in ovarian cancer cell line, SKOV-3x. Knocking Ape1 down had dramatic effects on cell growth in vitro but was not due to an increase in apoptosis and at least partially due to an extension in transit time through S-phase. Similarly, human ovarian tumor xenografts with reduced levels of Ape1 protein demonstrated a dramatic reduction in tumor volume (p < 0.01) and also statistically significant (p=0.02) differences in F-18-fluorodeoxyglucose (FDG) uptake indicating reduced glucose metabolism and cellular proliferation. Ape1's role in DNA repair and redox signaling is important to our basic understanding of ovarian cancer cell growth and these findings strongly support Ape1 as a therapeutic target. (c) 2007 Elsevier B.V. All rights reserved.
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