This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sengupta, P. K. Articles by Smith, B. D. Search for Related Content PubMed PubMed Citation Articles by Sengupta, P. K. Articles by Smith, B. D.

DNA Hypermethylation Near the Transcription Start Site of Collagen 2(I) Gene Occurs in Both Cancer Cell Lines and Primary Colorectal Cancers¹

Departments of Biochemistry [P. K. S., E. M. S., M. J. M., B. D. S.] and Pathology [M. J. M.], Boston University School of Medicine, Boston, Massachusetts; Boston VA Medical Center, Boston, Massachusetts [P. K. S., E. M. S., B. D. S.]; Mallory Institute of Pathology, Boston Medical Center, Boston, Massachusetts [M. J. M.]; and Chonnam University, South Korea [K. K.]

Collagen production plays a significant role in tumor development, especially in breast cancer, hepatocarcinomas, and colorectal carcinoma. However, collagen production is decreased during oncogenic transformation of cells in culture. This study demonstrates that methylation of the collagen 2(I) gene transcription start site occurs frequently in human cancer cell lines (9 of 10), including breast cancer cell lines (MCF-7 and Hs578T), hepatocellular carcinoma cell lines (SNU387, SNU449, SNU398, and PLC/PRF/5), a fibrosarcoma cell line (HT1080), and colorectal carcinoma cell lines (HCT116, SW480, and SW620). In addition, the collagen gene is more methylated in colorectal cancer tissues compared with normal mucosa. The increased DNA methylation of the collagen gene in cell lines is inversely correlated with collagen mRNA steady-state levels. Most importantly, treatment of fibrosarcoma or breast carcinoma cells with a DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine, resulted in lower methylation and reactivation of the collagen gene in a dose-responsive manner. This is the first demonstration that the collagen 2(I) gene is methylated in multiple cancer cell lines correlating with loss of collagen expression and also methylated in primary cancer tissues. These data also suggest that methylation-induced repression of collagen transcription may be a frequent occurrence in cancer.

This article has been cited by other articles:

				Y. Xu, J. A. Harton, and B. D. Smith CIITA Mediates Interferon-{gamma} Repression of Collagen Transcription through Phosphorylation-dependent Interactions with Co-repressor Molecules J. Biol. Chem., January 18, 2008; 283(3): 1243 - 1256. [Abstract] [Full Text] [PDF]

				J. A. Anderton, J. C. Lindsey, M. E. Lusher, R. J. Gilbertson, S. Bailey, D. W. Ellison, and S. C. Clifford Global analysis of the medulloblastoma epigenome identifies disease-subgroup-specific inactivation of COL1A2 Neuro-oncol, January 1, 2008; 10(6): 981 - 994. [Abstract] [Full Text] [PDF]

				V. Muthusamy, S. Duraisamy, C. M. Bradbury, C. Hobbs, D. P. Curley, B. Nelson, and M. Bosenberg Epigenetic Silencing of Novel Tumor Suppressors in Malignant Melanoma Cancer Res., December 1, 2006; 66(23): 11187 - 11193. [Abstract] [Full Text] [PDF]

				I. Ibanez de Caceres, E. Dulaimi, A. M. Hoffman, T. Al-Saleem, R. G. Uzzo, and P. Cairns Identification of novel target genes by an epigenetic reactivation screen of renal cancer. Cancer Res., May 15, 2006; 66(10): 5021 - 5028. [Abstract] [Full Text] [PDF]

				Y. Xu, P. K. Sengupta, E. Seto, and B. D. Smith Regulatory Factor for X-box Family Proteins Differentially Interact with Histone Deacetylases to Repress Collagen {alpha}2(I) Gene (COL1A2) Expression J. Biol. Chem., April 7, 2006; 281(14): 9260 - 9270. [Abstract] [Full Text] [PDF]

				R. van Doorn, W. H. Zoutman, R. Dijkman, R. X. de Menezes, S. Commandeur, A. A. Mulder, P. A. van der Velden, M. H. Vermeer, R. Willemze, P. S. Yan, et al. Epigenetic Profiling of Cutaneous T-Cell Lymphoma: Promoter Hypermethylation of Multiple Tumor Suppressor Genes Including BCL7a, PTPRG, and p73 J. Clin. Oncol., June 10, 2005; 23(17): 3886 - 3896. [Abstract] [Full Text] [PDF]

				P. Sengupta, Y. Xu, L. Wang, R. Widom, and B. D. Smith Collagen {alpha}1(I) Gene (COL1A1) Is Repressed by RFX Family J. Biol. Chem., June 3, 2005; 280(22): 21004 - 21014. [Abstract] [Full Text] [PDF]