Abstract：
:Melanoma differentiation associated gene-7/interleukin-24 (Mda-7/IL-24), a novel member of the IL-10 family of cytokines, uniquely displays cancer-specific apoptosis-inducing activity. Positive results in ongoing phase I/II clinical trials have strengthened the possibility of its utilization as a cancer gene therapeutic. Previous studies document that signaling events leading to Ad.mda-7-induced transformed cell apoptosis are tyrosine kinase-independent. These results suggest that mda-7/IL-24 cancer cell-specific activity could occur through mechanisms independent of binding to its currently recognized cognate receptors and might even occur independent of receptor function. An adenovirus vector expressing a nonsecreted version of MDA-7/IL-24 protein was generated via deletion of its signal peptide. This nonsecreted protein was as effective as wild-type secreted MDA-7/IL-24 in inducing apoptosis in prostate carcinoma cell lines and displayed transformed cell specificity and localization of MDA-7/IL-24 in the Golgi/endoplasmic reticulum compartments. Our results indicate that mda-7/IL-24-mediated apoptosis can be triggered through a combination of intracellular as well as secretory mechanisms and can occur efficiently in the absence of protein secretion.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Sauane M,Lebedeva IV,Su ZZ,Choo HT,Randolph A,Valerie K,Dent P,Gopalkrishnan RV,Fisher PBdoi
10.1158/0008-5472.can-04-0200subject
Has Abstractpub_date
2004-05-01 00:00:00pages
2988-93issue
9eissn
0008-5472issn
1538-7445journal_volume
64pub_type
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