Wild-type p53 suppresses transcription of the human O6-methylguanine-DNA methyltransferase gene

Linda C. Harris, Joanna S. Remack, Peter J Houghton, Thomas P. Brent

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

High-level expression of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) correlates with cellular resistance to the chloroethylnitrosourea (CENU) class of alkylating agents. Consequently, tumors expressing low levels of MGMT are sensitive to CENU chemotherapy, and any mechanism that can be used to reduce MGMT levels could sensitize resistant tumors. We have demonstrated that transient transfection of wild- type, but not mutant, p53 protein into a p53-null cell line, Saos-2, suppresses MGMT promoter activity in a reporter gene system. In addition, following a 24-h transduction of IMR90 fibroblasts with a wild-type p53- adenoviral vector, endogenous MGMT protein is down-regulated and is no longer detectable 5 days following infection. Because p53 is inducible by ionizing radiation, we propose that existing cancer therapy regimens that combine radiotherapy with CENU chemotherapy may be improved by altering scheduling and allowing enough time between the two therapies for the relatively stable MGMT protein to degrade.

Original languageEnglish (US)
Pages (from-to)2029-2032
Number of pages4
JournalCancer Research
Volume56
Issue number9
StatePublished - May 1 1996
Externally publishedYes

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Methyltransferases
DNA
Protein Methyltransferases
Genes
Drug Therapy
Null Lymphocytes
Neoplasms
Alkylating Agents
Mutant Proteins
Ionizing Radiation
Reporter Genes
DNA Repair
Transfection
O-(6)-methylguanine
Radiotherapy
Fibroblasts
Cell Line
Therapeutics
Infection
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Wild-type p53 suppresses transcription of the human O6-methylguanine-DNA methyltransferase gene. / Harris, Linda C.; Remack, Joanna S.; Houghton, Peter J; Brent, Thomas P.

In: Cancer Research, Vol. 56, No. 9, 01.05.1996, p. 2029-2032.

Research output: Contribution to journalArticle

Harris, Linda C. ; Remack, Joanna S. ; Houghton, Peter J ; Brent, Thomas P. / Wild-type p53 suppresses transcription of the human O6-methylguanine-DNA methyltransferase gene. In: Cancer Research. 1996 ; Vol. 56, No. 9. pp. 2029-2032.
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