Prostasin induces protease-dependent and independent molecular changes in the human prostate carcinoma cell line PC-3.
Expression of prostasin in the PC-3 human prostate carcinoma cells inhibited in vitro invasion, but the molecular mechanisms are unknown. Wild-type human prostasin or a serine active-site mutant prostasin was expressed in the PC-3 cells. Molecular changes were measured at the mRNA and the protein levels. Cell signaling changes were evaluated by measuring phosphorylation of the extracellular signal-regulated kinases (Erk1/2) following epidermal growth factor (EGF) treatment of the cells. Protein expression of the EGF receptor (EGFR) was differentially down-regulated by the wild-type and the active-site mutant prostasin. The mRNA expression of EGFR and the transcription repressor SLUG was reduced in cells expressing wild-type prostasin but not the active-site mutant. Phosphorylation of Erk1/2 in response to EGF was greatly reduced by the wild-type prostasin but not by the active-site mutant. The mRNA expression of the urokinase-type plasminogen activator (uPA), the uPA receptor (uPAR), cyclooxygenase-2 (COX-2), and the inducible nitric oxide synthase (iNOS) was decreased by the wild-type and the active-site mutant prostasin. The mRNA or protein expression of granulocyte-macrophage colony-stimulating factor (GM-CSF), matriptase, and E-cadherin was greatly increased by the active-site mutant prostasin. In conclusion, prostasin expression elicits both protease-dependent and independent molecular changes in the PC-3 cells.
Chen
Mengqian
M
Biomolecular Science Center, Burnett College of Biomedical Sciences, University of Central Florida, Orlando, FL 32816-2364, USA.
Fu
Ya-Yuan
YY
Lin
Chen-Yong
CY
Chen
Li-Mei
LM
Chai
Karl X
KX
D001665:Binding Sites; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D000099271:Prostasin
D015820:Cadherins; D051546:Cyclooxygenase 2; D066246:ErbB Receptors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008565:Membrane Proteins; D052247:Nitric Oxide Synthase Type II; D012697:Serine Endopeptidases; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014568:Urokinase-Type Plasminogen Activator; D000099271:Prostasin; C000604407:SNAI1 protein, human; C496540:PTGS2 protein, human; C485595:matriptase