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A Comparison of Human O⁶-Methylguanine-DNA Methyltransferase Promoter Activity in Mer⁺ and Mer^- Cells¹

Department of Biochemical and Clinical Pharmacology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101-0318

The activity of the human O⁶-methylguanine-DNA methyltransferase (MGMT) gene promoter was determined in eight human cell lines by measuring chloramphenicol acetyltransferase activity in a reporter gene system. MGMT promoter activities in cells that do not express MGMT (Mer^-) fell within the range of activities seen in cells that do express MGMT (Mer⁺). The promoter region contains 11 potential binding sites for the transcription factor Sp1, but no correlation was seen between cellular Sp1 protein and MGMT promoter chloramphenicol acetyltransferase activity. Because Mer^- cells are not deficient in the factors needed for transcription of MGMT, we suggest that at least two mechanisms regulate MGMT expression. One suppresses MGMT mRNA and protein in Mer^- cells, and another regulates the levels of constitutive expression in Mer⁺ cells. Sp1 is not a limiting factor in MGMT expression.

¹ This work was supported by NIH Grants CA 14799 and CA 23099 and by the American Lebanese Syrian Associated Charities.

² To whom requests for reprints should be addressed.

Received 9/15/92. Accepted 10/ 1/92.

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