PMID- 21887463
OWN - NLM
STAT- MEDLINE
DCOM- 20120703
LR  - 20231213
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 40
IP  - 3
DP  - 2012 Mar
TI  - Transcriptional analysis of CXCR4, DNMT3A, DNMT3B and DNMT1 gene expression in 
      primary advanced uterine cervical carcinoma.
PG  - 860-6
LID - 10.3892/ijo.2011.1183 [doi]
AB  - 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.
FAU - Luczak, Michal W
AU  - Luczak MW
AD  - Department of Biochemistry and Molecular Biology, Poznan University of Medical 
      Sciences, Poznan, Poland. mluc@ump.edu.pl
FAU - Roszak, Andrzej
AU  - Roszak A
FAU - Pawlik, Piotr
AU  - Pawlik P
FAU - Kedzia, Helena
AU  - Kedzia H
FAU - Kedzia, Witold
AU  - Kedzia W
FAU - Malkowska-Walczak, Blanka
AU  - Malkowska-Walczak B
FAU - Lianeri, Margarita
AU  - Lianeri M
FAU - Jagodzinski, Pawel P
AU  - Jagodzinski PP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110901
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (CXCR4 protein, human)
RN  - 0 (DNMT3A protein, human)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Receptors, CXCR4)
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1)
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases)
RN  - EC 2.1.1.37 (DNA Methyltransferase 3A)
RN  - EC 2.1.1.37 (DNMT1 protein, human)
SB  - IM
MH  - Cell Hypoxia/genetics
MH  - Cohort Studies
MH  - DNA (Cytosine-5-)-Methyltransferase 1
MH  - DNA (Cytosine-5-)-Methyltransferases/*genetics/metabolism
MH  - DNA Methylation
MH  - DNA Methyltransferase 3A
MH  - Epigenomics
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/*genetics
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism
MH  - Middle Aged
MH  - Promoter Regions, Genetic
MH  - Receptors, CXCR4/*genetics/metabolism
MH  - Transcription, Genetic
MH  - Uterine Cervical Neoplasms/*genetics/metabolism
MH  - DNA Methyltransferase 3B
EDAT- 2011/09/03 06:00
MHDA- 2012/07/04 06:00
CRDT- 2011/09/03 06:00
PHST- 2011/06/22 00:00 [received]
PHST- 2011/08/10 00:00 [accepted]
PHST- 2011/09/03 06:00 [entrez]
PHST- 2011/09/03 06:00 [pubmed]
PHST- 2012/07/04 06:00 [medline]
AID - 10.3892/ijo.2011.1183 [doi]
PST - ppublish
SO  - Int J Oncol. 2012 Mar;40(3):860-6. doi: 10.3892/ijo.2011.1183. Epub 2011 Sep 1.