Open AccessTranscriptional analysis of CXCR4, DNMT3A, DNMT3B and DNMT1 gene expression in primary advanced uterine cervical carcinoma
Author(s) -
Michał W. Łuczak,
Andrzej Roszak,
P. Pawlik,
H Kedzia,
Witold Kędzia,
Blanka Malkowska-Walczak,
Margarita Lianeri,
Paweł P. Jagodzińśki
Publication year - 2011
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo.2011.1183
Subject(s) - biology , dna methylation , cpg site , dnmt3b , cancer research , epigenetics , methylation , oncogene , promoter , cancer , carcinogenesis , microbiology and biotechnology , gene expression , gene , cell cycle , genetics
The development of cervical cancer requires genetic and epigenetic factorswhich result in the persistence of a malignant phenotype. Cervical cancer exhibitsalso some unique differences from other solid tumors. Normal cervical stratifiedepithelia have characteristics of hypoxic tissue with over-expression of HIF-1(hypoxia-inducible factor-1) transcription factor, which targets the transcriptionof 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 dinucleotideslocated in the promoter region. Here, we examined the CXCR4, DNMT3A, DNMT3B andDNMT1 transcript levels in cancer tissue (n=30) and non-cancer, normal uterinecervical tissue (n=30) from a Polish cohort. We also compared the methylationstatus of CXCR4 promoter region in cancer and normal tissue samples. Our resultshowed significantly higher levels of CXCR4, DNMT3A, DNMT3B and DNMT1 transcript(p=0.0058, 0.0163, 0.0003 and <0.0001, respectively) levels in cancer tissueas compared to normal samples. We did not observe DNA methylation in the CXCR4promoter region in either control or cancer tissue samples. CXCR4 has a functionalhypoxia response element (HRE) in the promoter region, located -1.3 kb from thetranscription start site. Our work shows for the first time that HIF-1A couldpromote the induction of CXCR4 gene expression (Spearman's correlation coefficient= 0.515, p=0.003) in patients with primary advanced uterine cervical carcinoma.