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Changes in genomic imprinting and gene expression associated with transformation in a model of human osteosarcoma
- Source :
- Experimental and Molecular Pathology. 84:234-239
- Publication Year :
- 2008
- Publisher :
- Elsevier BV, 2008.
-
Abstract
- Genomic imprinting, a heritable form of epigenetic information, is thought to play an important role in tumor progression. DNA methylation is a common mechanism of genomic imprinting. To evaluate the genome-wide effects of malignant transformation on osteosarcoma progression, we examined multiple biological properties, including DNA methylation, in human osteoblast hFOB1.19 cells (ATCC Catalog No. CRL-11372) transformed by treatment with carcinogenic agent N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG, 1.0 microg/ml) and carcinogenic promoting agent 12-O-tetradecanoyl phorbol-13-acetate (TPA, 200 ng/ml). We also examined global changes in expression of imprinted genes during transformation using microarray analysis. Ten imprinted genes, including H19, MKRN3, NDN, CDKN1C, PHLDA2, MEST, CD81, GRB10, SLC22A18, and SLC22A3 were aberrantly regulated in transformed cells, suggesting roles in tumorigenesis. Moreover, we analyzed the methylation state of the promoter regions of H19, PHLDA2, and SLC22A18 genes by bisulfite sequencing array and observed a correlation between upregulated expression of H19 and PHLDA2 genes and hypomethylation of their promoter regions, although this was not observed for SLC22A18. Our results suggest that changes in expression of imprinted genes caused by changes in methylation are involved, and are among the earliest events, in neoplastic progression.
- Subjects :
- Methylnitronitrosoguanidine
Clinical Biochemistry
Bisulfite sequencing
Bone Neoplasms
Biology
medicine.disease_cause
Cell Line
Pathology and Forensic Medicine
Genomic Imprinting
medicine
Humans
Epigenetics
Molecular Biology
Oligonucleotide Array Sequence Analysis
Regulation of gene expression
Osteosarcoma
Osteoblasts
Methylation
DNA Methylation
Molecular biology
Gene Expression Regulation, Neoplastic
Cell Transformation, Neoplastic
Tumor progression
DNA methylation
Carcinogens
Cancer research
Tetradecanoylphorbol Acetate
Genomic imprinting
Carcinogenesis
Subjects
Details
- ISSN :
- 00144800
- Volume :
- 84
- Database :
- OpenAIRE
- Journal :
- Experimental and Molecular Pathology
- Accession number :
- edsair.doi.dedup.....208576769aa9255eb573457d627e91bd