Dna methylation status of the MUC1 gene coding for a breast-cancer-associated protein

✍ Scribed by Sheila Zrihan-Licht; Mordechai Weiss; Iafa Keydar; Daniel H. Wreschner

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: French
• Weight: 865 KB
• Volume: 62
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910620303

✦ Synopsis

Abstract

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.