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Induction of morphological differentiation of human neuroblastoma cells is accompanied by induction of tissue‐type plasminogen activator
Author(s) -
Neuman T.,
Stephens R. W.,
Salonen E.M.,
Timmusk T.,
Vaheri A.
Publication year - 1989
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490230305
Subject(s) - retinoic acid , plasminogen activator , microbiology and biotechnology , northern blot , cellular differentiation , biology , neuroblastoma , phorbol , cell culture , activator (genetics) , urokinase , blot , messenger rna , chemistry , endocrinology , biochemistry , gene , enzyme , protein kinase c , genetics
Human SH‐SY5Y neuroblastoma cells treated with retinoic acid, 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA) or nerve growth factor differentiated morphologically to neuronlike cells with increased amounts of neurofilament protein and mRNA. All three effetors induced an increase in the amount of relative molecular weight (M r ) 70 000 tissue‐type plasminogen activator (t‐PA) and its mRNA, as determined by immunocapture, enzyme activity, and Northern blotting analyses. About 90% of the t‐PA activity was secreted to the culture medium. In contrast, of the three effectors studied, only TPA induced transcription of the proto‐oncogene c‐ fos , studied as a control gene responsive to various stimuli, and induced a rapid increase in urokinase‐type PA (u‐PA). Most of the u‐PA activity induced by TPA remained cell‐associated. Because induction of differentiation correlated closely with induction of t‐PA, and not u‐PA, the authors propose that t‐PA may have a functional role in the morphological differentiation of neuronal cells.