Loss of novel mda-7 splice variant (mda-7s) expression is associated with metastatic melanoma.
Expression of melanoma differentiation associated gene-7 (mda-7) also known as interleukin 24 (IL-24) decreases during melanoma cell differentiation and induces apoptosis in melanoma cells but not in melanocytes. Here we identify a novel splice variant of the cancer growth suppressor gene mda-7/IL-24 (mda-7s) that is differentially expressed in RNA preparations from normal human melanocytes, transformed melanocytes, nevi, subcutaneous metastasis, lymph node metastasis, and melanoma cell lines. The 450 bp mda-7s mRNA encodes a protein of 63 residues with a molecular weight of 12 kDa. mda-7s lacks exons 3 and 5 of the full-length transcript and contains only 14 amino acids of homology to MDA-7 located within the signal peptide region of the wild-type sequence. Despite minimal homology, MDA-7S coprecipitates full length MDA-7 and reduces secretion of cotransfected MDA-7. mda-7 and mda-7s are coexpressed in all RNA preparations other than subcutaneous and lymph node metastasis where mda-7s expression is lacking. mda-7s expression is therefore linked to a non-metastatic phenotype.
Department of Clinical Pharmacology, Section of Experimental Oncology/Molecular Pharmacology, University of Vienna, Vienna General Hospital, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Matthew
M
Allen
Barbara
B
Pratscher
Florian
F
Roka
Clemens
C
Krepler
Volker
V
Wacheck
Christian
C
Schöfer
Hubert
H
Pehamberger
Markus
M
Müller
Trevor
T
Lucas
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D019281:Dimerization; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007378:Interleukins / Q000737:chemistry / Q000235:genetics*; D008207:Lymphatic Metastasis; D008544:Melanocytes / Q000166:cytology / Q000502:physiology; D008545:Melanoma / Q000235:genetics* / Q000556:secondary; D008969:Molecular Sequence Data; D010641:Phenotype; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D000099180:Interleukin-24
D007378:Interleukins; D000099180:Interleukin-24