mda-7 (IL-24): signaling and functional roles.

Abstract

One hallmark of neoplasia is abnormal differentiation. Induction of differentiation, by chemical or biological methods, provides a possible therapeutic intervention. "Differentiation therapy" is well documented in several model systems. These include melanoma, in which treatment with interferon-beta and the protein kinase C activator mezerein induces irreversible growth arrest and terminal differentiation culminating in programmed cell death. Subtraction hybridization between terminally differentiated and untreated melanoma cells identified melanoma differentiation-associated gene-7 (mda-7), which is selectively induced during the process of melanoma terminal differentiation. Since its identification seven years ago, mda-7 has been the object of intense focus because of its unique biological properties. Firstly, mda-7 is a secreted protein having cytokine-like properties and belonging to the IL-10 cytokine family. Based on this consideration, mda-7 was renamed IL-24. Secondly if delivered by means of an adenoviral vector, mda-7 induces selective apoptosis in cancer cells of diverse origin, while sparing their normal cellular counterparts. As such, mda-7 has become a novel tool for cancer gene therapy and is currently undergoing phase II clinical trials to determine its clinical efficacy in patients. The present review examines the biological properties of mda-7 and the signaling pathways that contribute to its unique cancer-specific apoptosis-inducing properties.

• Authors: Devanand Sarkar, Zao-zhong Su, Irina V Lebedeva, Moira Sauane, Rahul V Gopalkrishnan, Paul Dent, Paul B Fisher
• Journal: BioTechniques (Biotechniques) Vol. Suppl Pg. 30-9 (Oct 2002) ISSN: 0736-6205 [Print] England
• PMID: 12395925 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Angiogenesis Inhibitors
• Interleukins
• Neoplasm Proteins
• Recombinant Fusion Proteins
• interleukin-24

Topics

• Angiogenesis Inhibitors (therapeutic use)
• Animals
• Apoptosis
• Cell Differentiation
• Chromosomes, Human, Pair 1 (genetics)
• Gene Expression Regulation, Neoplastic
• Genes, Tumor Suppressor
• Genetic Therapy
• Humans
• Interleukins (chemistry, genetics, physiology, therapeutic use)
• Mammals (genetics)
• Melanoma (genetics, metabolism, pathology)
• Mice
• Neoplasm Proteins (chemistry, genetics, physiology)
• Neoplasms (drug therapy, therapy)
• Pancreatic Neoplasms (genetics, pathology)
• Rats
• Recombinant Fusion Proteins (physiology)
• Safety
• Signal Transduction
• Tumor Cells, Cultured (pathology)