Journal
ONCOGENE
Volume 23, Issue 46, Pages 7679-7690Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1207958
Keywords
cancer gene therapy; GST-MDA-7/IL-24; apoptosis; breast cancer; radiotherapy
Funding
- NCI NIH HHS [CA88906, CA097318, CA098172] Funding Source: Medline
- NIDDK NIH HHS [DK52825] Funding Source: Medline
Ask authors/readers for more resources
The human mda-7/IL-24 gene product is normally expressed in melanocytes and certain lymphocyte populations. Loss of expression, a distinctive feature of many tumor suppressor genes, has been documented at RNA and protein levels in association with melanoma progression both in vitro as well as in human tumor-derived material. The MDA-7/IL-24 protein undergoes post-translational processing, including removal of an amino-terminal 48-residue signal peptide and extensive glycosylation prior to its secretion by producing cells. Its inherent cytokine properties have been documented in multiple reports, which have identified and characterized its cognate receptors and activation of the JAK/STAT signaling pathway following ligand/receptor docking. A notable and incompletely understood property of MDA-7/IL-24 is its ability to induce apoptosis in transformed cells, while having marginal growth suppressive effects on normal primary or immortalized cell lines. MDA-7/IL-24 has been delivered to cells, tumor xenografts and patients in clinical trials via a nonreplicating adenovirus (Ad.mda-7). Studies utilizing eukaryotically expressed and purified MDA-7/ IL-24 protein from several sources have recapitulated some of the molecule's reported properties including receptor binding and JAK/STAT activation. Here, we report the properties and characteristics of a bacterially expressed and purified GST-MDA-7 fusion protein. These studies reveal that GST-MDA-7 retains its cancer-selective apoptosis-inducing properties, thereby providing a new reagent that will assist in de. ning the mechanism of action of this novel cytokine. In addition, retention of tumor-specific activity of GST-MDA-7 suggests that this protein may also have therapeutic applications.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available