CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kuerbitz, S. J.
Right arrow Articles by Baylin, S. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kuerbitz, S. J.
Right arrow Articles by Baylin, S. B.

Cell Growth & Differentiation, Vol 7, Issue 6 847-853, Copyright © 1996 by American Association of Cancer Research


ARTICLES

Retention of unmethylated CpG island alleles in human diploid fibroblast x fibrosarcoma hybrids expressing high levels of DNA methyltransferase

SJ Kuerbitz and SB Baylin
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.

The mechanisms underlying ectopic methylation of CpG islands in neoplastic cells are poorly understood. One determinant may be the increased expression of DNA methyltransferase (DNA MTase) observed frequently in neoplastic cells. To evaluate the role of DNA MTase overexpression in aberrant CpG island methylation, we assessed methylation of fibroblast-derived CpG islands in human diploid fibroblast x fibrosarcoma hybrid cell lines. Each of six independently derived, immortalized hybrid cell lines exhibited a high level of DNA MTase expression, comparable to that of the fibrosarcoma parental line. The methylation status of five CpG island loci, each of which was methylated extensively in the fibrosarcoma parental cells but not in the fibroblasts, was then determined in the hybrid cell lines. The patterns of methylation were consistent and highly locus dependent among the hybrid lines. Unmethylated alleles were retained stably at three loci. The parental origin of alleles could be determined at two other loci in the hybrid cells. Whereas no methylation of parental fibroblast-derived alleles of the HIC-1 locus was noted in hybrid cell lines, a marked increase in methylation of fibroblast-derived alleles of the estrogen receptor was observed in all hybrid cell lines. Therefore, despite high-level DNA MTase expression, widespread loss of unmethylated CpG islands was not observed in the hybrid cell lines. The nonrandom pattern of increased CpG island methylation in the hybrid cell lines suggests that locus-specific features and/or clonal selection, and not just DNA MTase expression, affect the evolution of ectopic methylation in neoplastic cells. Somatic cell hybrids may provide useful models for studying aberrant epigenetic events in neoplastic cells.


This article has been cited by other articles:


Home page
EMBO J.Home page
S. Pradhan and G.-D. Kim
The retinoblastoma gene product interacts with maintenance human DNA (cytosine-5) methyltransferase and modulates its activity
EMBO J., February 15, 2002; 21(4): 779 - 788.
[Abstract] [Full Text] [PDF]


Home page
J. Cell Sci.Home page
J. R. MacDougall and L. M. Matrisian
Targets of extinction: identification of genes whose expression is repressed as a consequence of somatic fusion between cells representing basal and luminal mammary epithelial phenotypes
J. Cell Sci., February 1, 2000; 113(3): 409 - 423.
[Abstract] [PDF]


Home page
Cancer Res.Home page
P. G. Corn, S. J. Kuerbitz, M. M. van Noesel, M. Esteller, N. Compitello, S. B. Baylin, and J. G. Herman
Transcriptional Silencing of the p73 Gene in Acute Lymphoblastic Leukemia and Burkitt's Lymphoma Is Associated with 5' CpG Island Methylation
Cancer Res., July 1, 1999; 59(14): 3352 - 3356.
[Abstract] [Full Text] [PDF]


Home page
Cell Growth Differ.Home page
S. J. Kuerbitz, J. Malandro, N. Compitello, S. B. Baylin, and J. R. Graff
Deletion of p16INK4A/CDKN2 and p15INK4B in Human Somatic Cell Hybrids and Hybrid-derived Tumors
Cell Growth Differ., January 1, 1999; 10(1): 27 - 33.
[Abstract] [Full Text]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1996 by the American Association of Cancer Research.