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 II 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 microM 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 down-regulation 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.
journal_name
Proc Natl Acad Sci U S Aauthors
Kiaris H,Schally AVdoi
10.1073/pnas.96.1.226subject
Has Abstractpub_date
1999-01-05 00:00:00pages
226-31issue
1eissn
0027-8424issn
1091-6490journal_volume
96pub_type
杂志文章abstract::The growth of 3T3 and SV101 3T3 cells in a lipid-depleted medium is enhanced by the addition of biotin or some fatty acids. The extent of enhancement depends on the fatty acid(s) supplied. The presence of linoleate is unique, since it induces a morphological alteration in 3T3 cells resulting in a cell similar to an SV...
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