title: Transcriptional analysis of CXCR4, DNMT3A, DNMT3B and DNMT1 gene expression             in primary advanced uterine cervical carcinoma.
abstract: The development of cervical cancer requires genetic and epigenetic factors             which result in the persistence of a malignant phenotype. Cervical cancer exhibits             also some unique differences from other solid tumors. Normal cervical stratified             epithelia have characteristics of hypoxic tissue with over-expression of HIF-1             (hypoxia-inducible factor-1) transcription factor, which targets the transcription             of over 70 genes involved in many aspects of cancer biology. One of the genes,             which could be induced by HIF-1 is chemokine (C-X-C motif) receptor 4 (CXCR4).             CXCR4 could also be epigenetically regulated by methylation of CpG dinucleotides             located in the promoter region. Here, we examined the CXCR4, DNMT3A, DNMT3B and             DNMT1 transcript levels in cancer tissue (n=30) and non-cancer, normal uterine             cervical tissue (n=30) from a Polish cohort. We also compared the methylation             status of CXCR4 promoter region in cancer and normal tissue samples. Our result             showed significantly higher levels of CXCR4, DNMT3A, DNMT3B and DNMT1 transcript             (p=0.0058, 0.0163, 0.0003 and <0.0001, respectively) levels in cancer tissue             as compared to normal samples. We did not observe DNA methylation in the CXCR4             promoter region in either control or cancer tissue samples. CXCR4 has a functional             hypoxia response element (HRE) in the promoter region, located -1.3 kb from the             transcription start site. Our work shows for the first time that HIF-1A could             promote the induction of CXCR4 gene expression (Spearman's correlation coefficient             = 0.515, p=0.003) in patients with primary advanced uterine cervical carcinoma.
authors: Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań, Poland. mluc@ump.edu.pl
authors: Michał W
authors: MW
authors: Luczak
authors: Andrzej
authors: A
authors: Roszak
authors: Piotr
authors: P
authors: Pawlik
authors: Helena
authors: H
authors: Kędzia
authors: Witold
authors: W
authors: Kędzia
authors: Blanka
authors: B
authors: Malkowska-Walczak
authors: Margarita
authors: M
authors: Lianeri
authors: Paweł P
authors: PP
authors: Jagodziński
mesh_terms: D015687:Cell Hypoxia / Q000235:genetics; D015331:Cohort Studies; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D057890:Epigenomics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism; D000097584:DNA Methyltransferase 3B
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019718:Receptors, CXCR4; D000097584:DNA Methyltransferase 3B; C527276:CXCR4 protein, human; C000717967:DNMT3A protein, human; C497442:HIF1A protein, human; C000619380:DNMT1 protein, human