MDA-7/IL-24: novel cancer growth suppressing and apoptosis inducing cytokine.
The melanoma differentiation-associated gene-7 (mda-7) was cloned by subtraction hybridization as a molecule whose expression is elevated in terminally differentiated human melanoma cells. Current information based on structural and sequence homology, has led to the recognition of MDA-7 as an IL-10 family cytokine member and its renaming as IL-24. Northern blot analysis revealed mda-7/IL-24 expression in human tissues associated with the immune system such as spleen, thymus, peripheral blood leukocytes and normal melanocytes. The MDA-7/IL-24 mouse counterpart, FISP, appears to be a Th2-specific protein and the rat counterpart, C49A/MOB-5, is associated with wound healing and is also induced as a consequence of ras-transformation. A notable property of MDA-7/IL-24 is its ability to induce apoptosis in a large spectrum of human cancer derived cell lines, in mouse xenografts and upon intratumoral injection in human tumors (phase I clinical trials). Various aspects of this intriguing molecule including its cytokine and anti-tumoral effects are described and discussed.
Sauane
Moira
M
Department of Pathology, Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, BB-1501, 630 West 168th Street, New York, NY 10032, USA. ms2280@columbia.edu
Gopalkrishnan
Rahul V
RV
Sarkar
Devanand
D
Su
Zao Zhong
ZZ
Lebedeva
Irina V
IV
Dent
Paul
P
Pestka
Sidney
S
Fisher
Paul B
PB
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D000099180:Interleukin-24
D000970:Antineoplastic Agents; D016753:Interleukin-10; D007378:Interleukins; D000099180:Interleukin-24