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Reduced expression of PHD2 prolyl hydroxylase gene in primary advanced uterine cervical carcinoma
Andrzej Roszak1, Witold Kędzia, Blanka Malkowska-Walczak
1Department of Radiotherapy and Gynecological Oncology, Greater Poland Cancer Centre, Poznan, Poland.
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.
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