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Dna methylation status of the MUC 1 gene coding for a breast‐cancer‐associated protein
Author(s) -
ZrihanLicht Sheila,
Weiss Mordechai,
Keydar Iafa,
Wreschner Daniel H.
Publication year - 1995
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910620303
Subject(s) - dna methylation , biology , gene , cpg site , methylation , gene expression , regulation of gene expression , promoter , microbiology and biotechnology , breast cancer , epigenetics of physical exercise , cancer , dna , cancer research , genetics
The MUC 1 gene codes for protein products that are highly expressed in human breast‐cancer tissue and that serve as tumor markers for disease progression. The factors contributing to the disease‐specific over‐expression of the MUC 1 gene are under intensive investigation and are yet to be determined. A large transcribed region of the human MUCl gene is a CpG island that consists of 60‐bp tandemly repeating units, each of which contains one Smal restriction site. The methylation status of regulatory regions, upstream to the transcriptional start site, is essential for the regulation of gene expression. We therefore evaluated whether the methylation status of the various regions of the MUC 1 gene may affect its expression. Using Smal, and its isoschizomer Xmal endonucleases, we demonstrated that in peripheral‐blood leukocytes (PBL‐DNA) that do not express the MUC 1 gene, the repeat array is completely methylated, whereas the same sequences are entirely non‐methylated in breast‐tumor‐tissue DNA (BT‐DNA). In contrast, sequences upstream and downstream to the repeat array showed no difference in the methylation pattern in PBL‐DNA and BT‐DNA. Hypomethylation within the repeat array was also observed in other epithelial tissues that express the MUC 1 gene at much lower levels to those seen in breast‐cancer tissue. These studies demonstrate that hypomethylation of the tandem repeat array is an absolute requirement for MUC 1 gene expression in epithelial tissues, although in breast‐cancer tissue additional regulatory mechanisms must pertain for its over‐expression. © 1995 Wiley‐Liss Inc.