title: Reduced expression of PHD2 prolyl hydroxylase gene in primary advanced uterine cervical carcinoma.
abstract: Decreased PHD2 expression in human carcinomas has been considered a critical factor in supporting tumor angiogenesis and growth. We studied the levels of PHD2 transcript and protein in advanced cervical cancer specimens (n=27) and normal uterine cervical tissue samples (n=27). Real-time quantitative PCR and Western blotting analysis showed significantly lower levels of PHD2 transcript (P=0.0088) and protein (P=0.0095) in cancerous tissues as compared to corresponding normal tissue. Using DNA sequencing analysis, we also found an accumulation of mutations in promoter regions of PHD2 in advanced cervical cancer specimens. Moreover, computer analysis of these mutations showed a loss of binding sites for many transcription factors. Our results suggest PHD2 as a possible target in anti-angiogenic therapies in advanced uterine cervical carcinoma.
authors.affiliation: Department of Radiotherapy and Gynecological Oncology, Greater Poland Cancer Centre, Poznan, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Roszak
authors.forename: Witold
authors.initials: W
authors.lastname: Kędzia
authors.forename: Blanka
authors.initials: B
authors.lastname: Malkowska-Walczak
authors.forename: Piotr
authors.initials: P
authors.lastname: Pawlik
authors.forename: Helena
authors.initials: H
authors.lastname: Kędzia
authors.forename: Michał
authors.initials: M
authors.lastname: Łuczak
authors.forename: Margarita
authors.initials: M
authors.lastname: Lianeri
authors.forename: Paweł P
authors.initials: PP
authors.lastname: Jagodzinski
mesh_terms: D001665:Binding Sites; D015153:Blotting, Western; D015331:Cohort Studies; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism; D011393:Procollagen-Proline Dioxygenase / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012313:RNA / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D014157:Transcription Factors; D012313:RNA; C490190:EGLN1 protein, human; D011393:Procollagen-Proline Dioxygenase; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases