{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ray M"],"funding":["NCI NIH HHS"],"pagination":["846-55"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3401211"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["72(8)"],"pubmed_abstract":["<h4>Background</h4>In order for tumors to grow and proliferate, they must avoid recognition by immune cells and subsequent death by apoptosis. Granzyme B (GrB), a protease located in natural killer cells, initiates apoptosis in target cells. Inhibition of GrB by PI-9, its natural inhibitor, can prevent apoptosis. Here we investigate whether PI-9 protects prostate cancer cells from apoptosis.<h4>Methods</h4>The expression of PI-9 was quantified by qPCR in several prostate cancer cell lines, and GrB activity was tested in each cell line. PI-9 was overexpressed in LNCaP cells, which lack endogenous PI-9. Apoptosis was induced by natural killer cells in LNCaP cells that either contained or lacked PI-9, and the percent cell death was quantified. Lastly, PI-9 levels were examined by qPCR and immunohistochemistry in prostate tumor tissue.<h4>Results</h4>Prostate cancer cell lines that expressed PI-9 could inhibit GrB. Overexpression of PI-9 protected LNCaP cells from natural killer cell-mediated apoptosis. Examination of the levels of PI-9 in tissue from prostate tumors showed that PI-9 could be upregulated in low grade tumors and stochastically dysregulated in high grade tumors. Additionally, PI-9 was found consistently in high grade prostatic intraepithelial neoplasia and atrophic lesions.<h4>Conclusions</h4>These results indicate that overexpression of PI-9 can protect prostate cancer cells from apoptosis, and this effect may occur in human prostate tumors. These findings imply that early prostatic inflammation may trigger this increase in PI-9. This suggests that PI-9 upregulation is needed early in tumor progression, before additional protective mechanisms are in place."],"journal":["The Prostate"],"pubmed_title":["Inhibition of Granzyme B by PI-9 protects prostate cancer cells from apoptosis."],"pmcid":["PMC3401211"],"funding_grant_id":["R01 CA128765-03","R01 CA128765","R01CA128765"],"pubmed_authors":["Loeb CR","Simko J","Ray M","Hostetter DR","Craik CS"],"additional_accession":[]},"is_claimable":false,"name":"Inhibition of Granzyme B by PI-9 protects prostate cancer cells from apoptosis.","description":"<h4>Background</h4>In order for tumors to grow and proliferate, they must avoid recognition by immune cells and subsequent death by apoptosis. Granzyme B (GrB), a protease located in natural killer cells, initiates apoptosis in target cells. Inhibition of GrB by PI-9, its natural inhibitor, can prevent apoptosis. Here we investigate whether PI-9 protects prostate cancer cells from apoptosis.<h4>Methods</h4>The expression of PI-9 was quantified by qPCR in several prostate cancer cell lines, and GrB activity was tested in each cell line. PI-9 was overexpressed in LNCaP cells, which lack endogenous PI-9. Apoptosis was induced by natural killer cells in LNCaP cells that either contained or lacked PI-9, and the percent cell death was quantified. Lastly, PI-9 levels were examined by qPCR and immunohistochemistry in prostate tumor tissue.<h4>Results</h4>Prostate cancer cell lines that expressed PI-9 could inhibit GrB. Overexpression of PI-9 protected LNCaP cells from natural killer cell-mediated apoptosis. Examination of the levels of PI-9 in tissue from prostate tumors showed that PI-9 could be upregulated in low grade tumors and stochastically dysregulated in high grade tumors. Additionally, PI-9 was found consistently in high grade prostatic intraepithelial neoplasia and atrophic lesions.<h4>Conclusions</h4>These results indicate that overexpression of PI-9 can protect prostate cancer cells from apoptosis, and this effect may occur in human prostate tumors. These findings imply that early prostatic inflammation may trigger this increase in PI-9. This suggests that PI-9 upregulation is needed early in tumor progression, before additional protective mechanisms are in place.","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Jun","modification":"2025-04-04T21:17:43.433Z","creation":"2019-03-27T00:55:48Z"},"accession":"S-EPMC3401211","cross_references":{"pubmed":["21919028"],"doi":["10.1002/pros.21486"]}}