Document Detail

PROX1 overexpression inhibits protein kinase C beta II transcription through promoter DNA methylation.
MedLine Citation:
PMID:  22833470     Owner:  NLM     Status:  MEDLINE    
Prospero-related homeobox 1 (PROX1) is important for embryonic organ formation and differentiation, and changes in PROX1 activity were recently associated with cancer. To address the PROX1 roles in tumorigenesis, we established cells stably overexpressing PROX1 using the human cervical cancer cell line, HeLa. Overexpression of PROX1 reduced cell proliferation and the rate of tumor formation as compared with controls. Comparison of gene expression profiles between PROX1-overexpressing and mock-transfected cells revealed that the expression of protein kinase C βII (PRKCB2) is down-regulated in PROX1-overexpressing cells. A PRKCB inhibitor suppressed cell growth of control cells more than PROX1-expressing cells. Analysis of the 5'-promoter of PRKCB revealed that a region between -110 bp and the first exon contains two Sp1 binding sites and is important for transcriptional regulation of PRKCB. The inhibition of Sp1 transcription factor resulted in down-regulation of PRKCB2 protein levels. Treatment with a demethylating agent, 5-aza-2'-deoxycytidine, restored PRKCB2 mRNA expression in PROX1-expressing cells, suggesting that the 5'-promoter of PRKCB is methylated in these cells. Actually, it was found that a CpG island in this region, in particular a CpG site overlapping with the distal Sp1 site, was hypermethylated and direct Sp1 binding to this region was inhibited in PROX1-overexpressing cells. Thus, the suppressive effect of PROX1 on cell growth and tumor formation might be partially mediated by PRKCB2 via altered methylation of its promoter.
Kazumi Hagiwara; Hiromi Ito; Takashi Murate; Yasuhiko Miyata; Haruhiko Ohashi; Hirokazu Nagai
Publication Detail:
Type:  Journal Article     Date:  2012-07-25
Journal Detail:
Title:  Genes, chromosomes & cancer     Volume:  51     ISSN:  1098-2264     ISO Abbreviation:  Genes Chromosomes Cancer     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-09-10     Completed Date:  2013-03-29     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  9007329     Medline TA:  Genes Chromosomes Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1024-36     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
Department of Hematology/Oncology Research, Clinical Research Center, National Hospital Organization Nagoya Medical Center, Japan.
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MeSH Terms
Azacitidine / analogs & derivatives,  pharmacology
Cell Proliferation / drug effects
DNA Methylation*
Down-Regulation / drug effects
Gene Expression Profiling
HCT116 Cells
HeLa Cells
Homeodomain Proteins / biosynthesis*,  genetics*,  metabolism
Indoles / pharmacology
Mice, Inbred BALB C
Oligonucleotide Array Sequence Analysis
Promoter Regions, Genetic
Protein Kinase C / antagonists & inhibitors,  genetics*,  metabolism
Sp1 Transcription Factor / antagonists & inhibitors,  metabolism
Tumor Suppressor Proteins / biosynthesis*,  genetics*,  metabolism
Reg. No./Substance:
0/Homeodomain Proteins; 0/Indoles; 0/Sp1 Transcription Factor; 0/Tumor Suppressor Proteins; 0/prospero-related homeobox 1 protein; 320-67-2/Azacitidine; 776B62CQ27/decitabine; EC 2.7.1.-/protein kinase C beta; EC Kinase C; UC96G28EQF/enzastaurin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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