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Cytosine methylation and suppression of O6-methylguanine-DNA methyltransferase expression in human rhabdomyosarcoma cell lines and xenografts.

Publication ,  Journal Article
von Wronski, MA; Harris, LC; Tano, K; Mitra, S; Bigner, DD; Brent, TP
Published in: Oncol Res
1992

Human tumor cell lines that do not express O6-methylguanine-DNA methyltransferase (MGMT) in detectable quantities (Mer-) are hypersensitive to the effects of O6-guanine-alkylating agents. Because the Mer- phenotype enhances tumor response to such agents, we investigated possible mechanisms involved in regulation of MGMT expression in a panel of Mer+ and Mer- pediatric rhabdomyosarcoma xenograft and cell lines. All Mer- cell and xenograft lines lacked not only MGMT activity but also the protein and mRNA as well, suggesting that its expression is transcriptionally regulated. Transfection of Mer+ and Mer- rhabdomyosarcoma cell lines with MGMT gene promoter-CAT constructs yielded similar levels of CAT expression, indicating that Mer- cells possessed the necessary factors to support transcription. Methylation in the 5'-untranslated region of the MGMT gene was assayed by Southern analysis using methylation-sensitive restriction enzymes. Digestion with HpaII and its methylation-insensitive isoschizomer, MspI, revealed little overall correlation between methylation and MGMT expression. However, methylation in a single SmaI site at position-69 was observed in all MGMT deficient lines but not in any MGMT expressing lines. These results suggest that methylation of specific cytosines in the MGMT promoter may play a role in suppressing its expression, as well as being a potentially useful marker for the Mer- phenotype.

Duke Scholars

Published In

Oncol Res

ISSN

0965-0407

Publication Date

1992

Volume

4

Issue

4-5

Start / End Page

167 / 174

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Suppression, Genetic
  • Rhabdomyosarcoma
  • RNA, Messenger
  • Promoter Regions, Genetic
  • Oncology & Carcinogenesis
  • O(6)-Methylguanine-DNA Methyltransferase
  • Neoplasm Transplantation
  • Mice
 

Citation

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ICMJE
MLA
NLM
von Wronski, M. A., Harris, L. C., Tano, K., Mitra, S., Bigner, D. D., & Brent, T. P. (1992). Cytosine methylation and suppression of O6-methylguanine-DNA methyltransferase expression in human rhabdomyosarcoma cell lines and xenografts. Oncol Res, 4(4–5), 167–174.
Wronski, M. A. von, L. C. Harris, K. Tano, S. Mitra, D. D. Bigner, and T. P. Brent. “Cytosine methylation and suppression of O6-methylguanine-DNA methyltransferase expression in human rhabdomyosarcoma cell lines and xenografts.Oncol Res 4, no. 4–5 (1992): 167–74.
von Wronski MA, Harris LC, Tano K, Mitra S, Bigner DD, Brent TP. Cytosine methylation and suppression of O6-methylguanine-DNA methyltransferase expression in human rhabdomyosarcoma cell lines and xenografts. Oncol Res. 1992;4(4–5):167–74.
von Wronski MA, Harris LC, Tano K, Mitra S, Bigner DD, Brent TP. Cytosine methylation and suppression of O6-methylguanine-DNA methyltransferase expression in human rhabdomyosarcoma cell lines and xenografts. Oncol Res. 1992;4(4–5):167–174.
Journal cover image

Published In

Oncol Res

ISSN

0965-0407

Publication Date

1992

Volume

4

Issue

4-5

Start / End Page

167 / 174

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Suppression, Genetic
  • Rhabdomyosarcoma
  • RNA, Messenger
  • Promoter Regions, Genetic
  • Oncology & Carcinogenesis
  • O(6)-Methylguanine-DNA Methyltransferase
  • Neoplasm Transplantation
  • Mice