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Asian Journal of Andrology ; (6): 147-158, 2005.
Article in English | WPRIM | ID: wpr-270858

ABSTRACT

<p><b>AIM</b>To determine the effect of saposin C (a known trophic domain of prosaposin) on proliferation, migration and invasion, as well as its effect on the expression of urokinase plasmonogen activator (uPA), its receptor (uPAR) and matrix metalloproteinases (MMP)-2 and -9 in normal and malignant prostate cells. In addition, we tested whether saposin C can activate p42/44 and stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) signal transduction pathways of the mitogen-activated protein kinase (MAPK) superfamily.</p><p><b>METHODS</b>We employed Western blot analysis, phospho-specific antibodies, cell proliferation assay, reverse transcriptase-polymerase chain reaction, in vitro kinase assays and migration and invasion to determine the effect of saposin C on various biological behaviors of prostate stromal and cancer cells.</p><p><b>RESULTS</b>Saposin C, in a cell type-specific manner, upregulates uPA/uPAR and immediate early gene c-Jun expression, stimulates cell proliferation, migration and invasion and activates p42/44 and SAPK/JNK MAPK pathways in prostate stromal and cancer cells. Normal prostate epithelial cells were not responsive to saposin C treatment in the above studies.</p><p><b>CONCLUSION</b>Saposin C functions as a multipotential modulator of diverse biological activities in prostate cancer and stromal cells. These results strongly suggest that saposin C functions as a potent growth factor for prostatic cells and may contribute to prostate carcinogenesis and/or the development of hormone-refractory prostate cancer.</p>


Subject(s)
Humans , Male , Cell Division , Enzyme Activation , Mitogen-Activated Protein Kinases , Metabolism , Neoplasm Invasiveness , Prostatic Neoplasms , Metabolism , Pathology , Receptors, Cell Surface , Genetics , Receptors, Urokinase Plasminogen Activator , Reverse Transcriptase Polymerase Chain Reaction , Saposins , Pharmacology , Signal Transduction , Stromal Cells , Metabolism , Pathology , Up-Regulation , Urokinase-Type Plasminogen Activator , Genetics
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