Decrease in telomerase activity in U-87MG human glioblastomas after treatment with an antagonist of growth hormone-releasing hormone

Hippokratis Kiaris, Andrew V. Schally

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Antagonists of growth hormone-releasing hormone (GH-RH) inhibit the growth of various tumors through mechanisms that involve the suppression of the insulin-like growth factor I and/or insulin-like growth factor H levels or secretion. In the present study, we tested the hypothesis that the tumor inhibition is associated with a decrease in telomerase activity because telomerase is considered obligatory for continued tumor growth. Nude mice bearing xenografts of U-87MG human glioblastomas were treated with GH-RH antagonist MZ-5-156. Telomerase activity was assessed by the telomerase repeat amplification protocol. Treatment with MZ-5-156 reduced levels of telomerase activity as compared with controls. When U-87 glioblastomas, H-69 small cell lung carcinomas, H-23 non-small cell lung carcinomas, and MDA-MB- 468 breast carcinoma cells were cultured in vitro, addition of 3 μM MZ-5- 156 also inhibited telomerase activity. Reverse transcription-PCR analysis revealed that in U-87MG glioblastomas, the expression of the hTRT gene encoding for the telomerase catalytic subunit was significantly decreased by MZ-5-156, whereas the levels of mRNA for hTR and TP1, which encode for the telomerase RNA and telomerase-associated protein, respectively, were unaffected. The repression of the telomerase activity was not accompanied by a significant decrease of mRNA level for the c-myc protooncogene that regulates telomerase. Our findings suggest that tumor inhibition induced by the GH-RH antagonists in U-87MG glioblastomas is associated with the downregulation of the hTRT gene, resulting in a decrease in telomerase activity. Further studies are needed to establish whether GH-RH antagonists produce telomerase inhibition in other tumors.

Original languageEnglish (US)
Pages (from-to)226-231
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number1
DOIs
StatePublished - Jan 5 1999
Externally publishedYes

Keywords

  • Down-regulation of telomerase gene
  • Telomerase catalytic subunit regulation
  • Telomerase repeat amplification assay
  • Tumor regression

ASJC Scopus subject areas

  • Genetics
  • General

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