Selective suppression of cathepsin L by antisense cDNA impairs human brain tumor cell invasion in vitro and promotes apoptosis
| Autor: | Tamara T. Lah, Ricardo A Dewey, Emma Daley, Nataša Levičar, Derek Davies, Janko Kos, Timothy E. Bates, Geoffrey J. Pilkington |
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| Rok vydání: | 2003 |
| Předmět: |
Cancer Research
DNA Complementary Cathepsin L Cathepsin D Apoptosis DNA Antisense Cell Movement Sense (molecular biology) Cell Adhesion Tumor Cells Cultured medicine Humans Staurosporine Neoplasm Invasiveness Molecular Biology Cathepsin S Cathepsin biology Brain Neoplasms Caspase 3 Genetic Therapy Cathepsins Molecular biology Cysteine Endopeptidases Proto-Oncogene Proteins c-bcl-2 Cell culture Caspases biology.protein Molecular Medicine Glioblastoma Cell Division medicine.drug |
| Zdroj: | Cancer Gene Therapy. 10:141-151 |
| ISSN: | 1476-5500 0929-1903 |
| DOI: | 10.1038/sj.cgt.7700546 |
| Popis: | Invasion and metastasis of certain tumors are accompanied by increased mRNA protein levels and enzymatic activity of cathepsin L. Cathepsin L has also been suggested to play a role in the proteolytic cascades associated with apoptosis. To investigate the role of cathepsin L in brain tumor invasion and apoptosis, the human glioma cell line, IPTP, was stably transfected with full-length antisense and sense cDNA of cathepsin L. Down-regulation of cathepsin L by antisense cDNA significantly impaired (up to 70%) glioma cell invasion in vitro and markedly increased glioma cell apoptosis induced by staurosporine. Compared to control and parental cell lines, antisense down-regulation of cathepsin L was associated with an earlier induction of caspase-3 activity. Up-regulation of cathepsin L activity by sense cDNA was associated with reduced apoptosis and later induction of caspase-3 activity. Moreover, down-regulation of cathepsin L lowered the expression of antiapoptotic protein Bcl-2, whereas up-regulation increased the expression of Bcl-2, indicating that cathepsin L acts upstream of caspase-3. These data show that cathepsin L is an important protein mediating the malignancy of gliomas and its inhibition may diminish their invasion and lead to increased tumor cell apoptosis by reducing apoptotic threshold. |
| Databáze: | OpenAIRE |
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