| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Advances in Brief |
Departments of Pathology [A. M. D., V. L. M.], Oncology [E. S. Y., R. V., X. L., W. G. N.], Urology [E. S. Y., R. V., X. L., W. G. N.], Pharmacology [W. G. N.], and Medicine [W. G. N.], The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287
Somatic changes in CpG dinucleotide methylation occur quite commonly in human cancer cell DNA. Relative to DNA from normal human colonic cells, DNA from human colorectal cancer cells typically displays regional CpG dinucleotide hypermethylation amid global CpG dinucleotide hypomethylation. The role of the maintenance DNA methyltransferase (DNMT1) in the acquisition of such abnormal CpG dinucleotide methylation changes in colorectal cancer cells remains controversial; in one study, 60–200-fold increases in DNMT1 mRNA expression were detected in colorectal polyps and cancers relative to normal colonic tissue [W. S. El-Deiry et al., Proc. Natl. Acad. Sci. USA, 88: 3470–3474, 1991], whereas in another study, only small increases in DNMT1 mRNA expression, commensurate with differences in cell proliferation accompanying colonic tumorigenesis, were observed [P. J. Lee et al., Proc. Natl. Acad. Sci. USA, 93: 10366–10370, 1996]. To definitively ascertain whether abnormal DNMT1 expression might accompany human colorectal carcinogenesis, we subjected a series of normal and neoplastic colonic tissues to immunohistochemical staining using a polyclonal antiserum raised against a DNMT1 polypeptide. A concordance of DNMT1 expression with the expression of PCNA and other cell proliferation markers, such as Ki-67 and DNA topoisomerase II
, was observed in normal colonic epithelial cells and in cells comprising other normal epithelia and lymphoid tissues. The polypeptide p21, which has been reported to undermine DNMT1 binding to proliferating cell nuclear antigen at DNA replication sites, was not expressed by normal colonic cells containing DNMT1 and other cell proliferation markers. In adenomatous polyps, although DNMT1 expression coincided with the expression of other cell proliferation markers, many DNMT1-expressing cells also expressed p21. The fidelity of DNMT1 expression was further undermined in colorectal carcinomas, in which a striking heterogeneity in DNMT1 expression, with some carcinoma cells containing very high DNMT1 levels and others containing very low DNMT1 levels, was observed. These results indicate that human colorectal carcinogenesis is accompanied by a progressive dysregulation of DNMT1 expression and suggest that abnormalities in DNMT1 expression may contribute to the abnormal CpG dinucleotide methylation changes characteristic of human colorectal carcinoma cell DNA.
This article has been cited by other articles:
|
|
 |
|
  W. G. Nelson, A. M. De Marzo, and S. Yegnasubramanian Epigenetic Alterations in Human Prostate Cancers Endocrinology, September 1, 2009; 150(9): 3991 - 4002. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ruzov, B. Shorning, O. Mortusewicz, D. S. Dunican, H. Leonhardt, and R. R. Meehan MBD4 and MLH1 are required for apoptotic induction in xDNMT1-depleted embryos Development, July 1, 2009; 136(13): 2277 - 2286. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. K. Jung, P. Arora, J. S. Pagano, and K. L. Jang Expression of DNA Methyltransferase 1 Is Activated by Hepatitis B Virus X Protein via a Regulatory Circuit Involving the p16INK4a-Cyclin D1-CDK 4/6-pRb-E2F1 Pathway Cancer Res., June 15, 2007; 67(12): 5771 - 5778. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. T. Agoston, P. Argani, A. M. De Marzo, J. L. Hicks, and W. G. Nelson Retinoblastoma Pathway Dysregulation Causes DNA Methyltransferase 1 Overexpression in Cancer via MAD2-Mediated Inhibition of the Anaphase-Promoting Complex Am. J. Pathol., May 1, 2007; 170(5): 1585 - 1593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Miremadi, M. Z. Oestergaard, P. D.P. Pharoah, and C. Caldas Cancer genetics of epigenetic genes Hum. Mol. Genet., April 15, 2007; 16(R1): R28 - R49. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Khan, F. Afaq, M.-H. Kweon, K. Kim, and H. Mukhtar Oral Consumption of Pomegranate Fruit Extract Inhibits Growth and Progression of Primary Lung Tumors in Mice Cancer Res., April 1, 2007; 67(7): 3475 - 3482. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Torrisani, A. Unterberger, S. R. Tendulkar, K. Shikimi, and M. Szyf AUF1 Cell Cycle Variations Define Genomic DNA Methylation by Regulation of DNMT1 mRNA Stability Mol. Cell. Biol., January 1, 2007; 27(1): 395 - 410. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Ting, K. M. McGarvey, and S. B. Baylin The cancer epigenome--components and functional correlates Genes & Dev., December 1, 2006; 20(23): 3215 - 3231. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Sharma, J. Blum, X. Yang, N. Beaulieu, A. R. Macleod, and N. E. Davidson Release of Methyl CpG Binding Proteins and Histone Deacetylase 1 from the Estrogen Receptor {alpha} (ER) Promoter upon Reactivation in ER-Negative Human Breast Cancer Cells Mol. Endocrinol., July 1, 2005; 19(7): 1740 - 1751. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. T. Agoston, P. Argani, S. Yegnasubramanian, A. M. De Marzo, M. A. Ansari-Lari, J. L. Hicks, N. E. Davidson, and W. G. Nelson Increased Protein Stability Causes DNA Methyltransferase 1 Dysregulation in Breast Cancer J. Biol. Chem., May 6, 2005; 280(18): 18302 - 18310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Lund and M. van Lohuizen Epigenetics and cancer Genes & Dev., October 1, 2004; 18(19): 2315 - 2335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Etoh, Y. Kanai, S. Ushijima, T. Nakagawa, Y. Nakanishi, M. Sasako, S. Kitano, and S. Hirohashi Increased DNA Methyltransferase 1 (DNMT1) Protein Expression Correlates Significantly with Poorer Tumor Differentiation and Frequent DNA Hypermethylation of Multiple CpG Islands in Gastric Cancers Am. J. Pathol., February 1, 2004; 164(2): 689 - 699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Fahrner and S. B. Baylin Heterochromatin: stable and unstable invasions at home and abroad Genes & Dev., August 1, 2003; 17(15): 1805 - 1812. [Full Text] [PDF]
|
|
|
|
|
|
X. Lin and W. G. Nelson Methyl-CpG-binding Domain Protein-2 Mediates Transcriptional Repression Associated with Hypermethylated GSTP1 CpG Islands in MCF-7 Breast Cancer Cells Cancer Res., January 15, 2003; 63(2): 498 - 504. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Goffin and E. Eisenhauer DNA methyltransferase inhibitors--state of the art Ann. Onc., November 1, 2002; 13(11): 1699 - 1716. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Davis and E. O. Uthus Dietary Selenite and Azadeoxycytidine Treatments Affect Dimethylhydrazine-Induced Aberrant Crypt Formation in Rat Colon and DNA Methylation in HT-29 Cells J. Nutr., February 1, 2002; 132(2): 292 - 297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Hodge, W. Xiao, P. A. Clausen, G. Heidecker, M. Szyf, and W. L. Farrar Interleukin-6 Regulation of the Human DNA Methyltransferase (HDNMT) Gene in Human Erythroleukemia Cells J. Biol. Chem., October 19, 2001; 276(43): 39508 - 39511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Osanai, W. Ichikawa, Y. Takagi, H. Uetake, Z. Nihei, and K. Sugihara Expression of Pyrimidine Nucleoside Phosphorylase (PyNPase) in Colorectal Cancer Jpn. J. Clin. Oncol., October 1, 2001; 31(10): 500 - 505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Lin, S.-Y. Hsieh, I-S. Sheen, W.-C. Lee, T.-C. Chen, W.-C. Shyu, and Y.-F. Liaw Genome-wide Hypomethylation in Hepatocellular Carcinogenesis Cancer Res., May 1, 2001; 61(10): 4238 - 4243. [Abstract] [Full Text]
|
|
|
|
|
|
Q. Zhang, P. N. Raghunath, E. Vonderheid, N. Odum, and M. A. Wasik Lack of Phosphotyrosine Phosphatase SHP-1 Expression in Malignant T-Cell Lymphoma Cells Results from Methylation of the SHP-1 Promoter Am. J. Pathol., October 1, 2000; 157(4): 1137 - 1146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T. Cormier and W. F. Dove Dnmt1N/+ Reduces the Net Growth Rate and Multiplicity of Intestinal Adenomas in C57BL/6-Multiple Intestinal Neoplasia (Min)/+ Mice Independently of p53 but Demonstrates Strong Synergy with the Modifier of Min 1AKR Resistance Allele Cancer Res., July 1, 2000; 60(14): 3965 - 3970. [Abstract] [Full Text]
|
|
|
|
|
|
N. Detich, S. Ramchandani, and M. Szyf A Conserved 3'-Untranslated Element Mediates Growth Regulation of DNA Methyltransferase 1 and Inhibits Its Transforming Activity J. Biol. Chem., June 29, 2001; 276(27): 24881 - 24890. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
