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Cyclosporin A inhibits growth of autocrine tumour cell lines by destabilizing interleukin-3 mRNA

Nair, A. P. and Hahn, S. and Banholzer, R. and Hirsch, H. H. and Moroni, C.. (1994) Cyclosporin A inhibits growth of autocrine tumour cell lines by destabilizing interleukin-3 mRNA. Nature, Vol. 369. pp. 239-242.

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Official URL: http://edoc.unibas.ch/dok/A5257897

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Abstract

In T cells, cyclosporin A (CsA) exerts its immunosuppressive effect by preventing transcriptional induction of the expression of interleukin(IL)-2. This is achieved by a mechanism that involves binding of a CsA-cyclophilin complex to calcineurin, which in turn inhibits the phosphatase-controlled translocation of transcription factor NFAT to the nucleus. We have previously identified IL-3 as an autocrine oncogenic regulator in tumour cell lines generated by introducing the v-H-ras oncogene into IL-3-dependent mast cells. Here we report that CsA specifically blocks autocrine tumour cell growth. The mechanism involves down-regulation of IL-3 expression by destabilization of the messenger RNA and requires ongoing transcription. Transcripts from exogenous IL-3 genes lacking the (A+U)-rich element (ARE) in the 3' untranslated terminal repeat could not be destabilized, suggesting that at least part of this sequence, which is known to mediate decay of short-lived mRNA, participates in a CsA-sensitive regulatory mechanism.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Growth and Development (Moroni)
03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Growth and Development (Moroni)
UniBasel Contributors:Moroni, Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Macmillan
ISSN:0028-0836
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:22 Mar 2012 14:20
Deposited On:22 Mar 2012 13:19

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