title: DNA repair-redox enzyme apurinic endonuclease in cervical cancer: evaluation of redox control of HIF-1alpha and prognostic significance.
abstract: The multifunctional apurinic/apyrimidinic endonuclease (Ape1/ref-1) plays a key role in the human DNA base excision repair pathway. Ape1/ref-1 has also been shown to be involved in the redox control of transactivation activities of hypoxia-inducible factor (HIF)-1alpha. The aim of our study was to investigate the expression of these proteins in early stage invasive cervical cancer. Expression of Ape1/ref-1 and HIF-1alpha was detected immunohistochemically in 88 samples of cervical cancer stage pT1b. The levels of the proteins were compared and the prognostic influence of Ape1/ref-1 expression was investigated. Strong nuclear expression of Ape1/ref-1 was observed in 9 cases (10.2%), moderate in 22 cases (25%), weak in 17 cases (19.3%), and absent in 40 cases (45.5%). Furthermore, no correlation between Ape1/ref-1 and HIF-1alpha expression was observed (p=0.864). We also found no relationship of Ape1/ref-1 expression and survival (p>0.05, log-rank test). From these studies, we have concluded that in cervical cancer there is no correlation between the upstream redox regulatory protein of HIF-1, i.e., Ape1/ref-1, and HIF-1alpha expression. However, these studies do not address any functional relationship between the two proteins.
authors.affiliation: Institute of Clinical Pathology, University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Schindl
authors.forename: G
authors.initials: G
authors.lastname: Oberhuber
authors.forename: E G
authors.initials: EG
authors.lastname: Pichlbauer
authors.forename: A
authors.initials: A
authors.lastname: Obermair
authors.forename: P
authors.initials: P
authors.lastname: Birner
authors.forename: M R
authors.initials: MR
authors.lastname: Kelley
mesh_terms: D019757:Carbon-Oxygen Lyases / Q000378:metabolism*; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D005260:Female; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007124:Immunoenzyme Techniques; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D011379:Prognosis; D014157:Transcription Factors; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors; D004706:Endodeoxyribonucleases; D019757:Carbon-Oxygen Lyases; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase