Cloning of a novel malignant melanoma-derived growth-regulatory protein, MIA.
Growth and progression of malignant melanoma cells is influenced by a complex network of growth-stimulating and -inhibiting factors produced by both the tumor cells and the local environment. Here we report the purification and molecular cloning of a novel growth regulating protein, designated melanoma inhibitory activity (MIA) and provide a preliminary functional characterization. MIA is translated as a 131-amino acid precursor and processed into a mature 107-amino acid protein after cleavage of a putative secretion signal. A murine complementary DNA was isolated that encoded a MIA-protein with 88% amino acid identity. MIA is secreted into the culture supernatant by several malignant melanoma cell lines as an M(r) 11,000 autocrine growth factor and acts as a potent tumor cell growth inhibitor for malignant melanoma cells and some other neuroectodermal tumors, including gliomas. MIA has no homology to any other known protein and, therefore, represents a novel type of growth-regulatory factor. Furthermore, we describe a molecular approach to express functionally active MIA in Escherichia coli, which might be attractive as a future antitumor therapeutical substance.
Blesch
A
A
Department of Neurology, University of Würzburg, Federal Republic of Germany.
Bosserhoff
A K
AK
Apfel
R
R
Behl
C
C
Hessdoerfer
B
B
Schmitt
A
A
Jachimczak
P
P
Lottspeich
F
F
Buettner
R
R
Bogdahn
U
U
D000595:Amino Acid Sequence; D001483:Base Sequence; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D016326:Extracellular Matrix Proteins; D006801:Humans; D008545:Melanoma / Q000737:chemistry*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification*; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D016326:Extracellular Matrix Proteins; C090059:MIA protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins