Show simple item record Misra, UK Pizzo, SV
dc.coverage.spatial United States 2011-06-21T17:21:59Z 2010-01
dc.identifier 10422
dc.identifier.citation Cancer Biol Ther, 2010, 9 (2), pp. 142 - 152
dc.description.abstract We have previously shown that treatment of prostate cancer and melanoma cells expressing GRP78 on their cell surface with antibody directed against the COOH-terminal domain of GRP78 upregulates and activates p53 causing decreased cell proliferation and upregulated apoptosis. In this report, we demonstrate that treatment of 1-LN prostate cancer cells with this antibody decreases cell surface expression of GRP78, Akt(Thr308) and Akt(Ser473) kinase activities and reduces phosphorylation of FOXO, and GSK3beta. This treatment also suppresses activation of ERK1/2, p38 MAPK and MKK3/6; however, it upregulates MKK4 activity. JNK, as determined by its phosphorylation state, is subsequently activated, triggering apoptosis. Incubation of cells with antibody reduced levels of anti-apoptotic Bcl-2, while elevating pro-apoptotic BAD, BAX and BAK expression as well as cleaved caspases-3, -7, -8 and -9. Silencing GRP78 or p53 gene expression by RNAi prior to antibody treatment abrogated these effects. We conclude that antibody directed against the COOH-terminal domain of GRP78 may prove useful as a pan suppressor of proliferative/survival signaling in cancer cells expressing GRP78 on their cell surface.
dc.format.extent 142 - 152
dc.language eng
dc.language.iso en_US en_US
dc.relation.ispartof Cancer Biol Ther
dc.subject Adenocarcinoma
dc.subject Amino Acid Sequence
dc.subject Antibodies, Monoclonal
dc.subject Antigens, Neoplasm
dc.subject Antigens, Surface
dc.subject Caspases
dc.subject Cell Line, Tumor
dc.subject Enzyme Activation
dc.subject Gene Knockdown Techniques
dc.subject Heat-Shock Proteins
dc.subject Humans
dc.subject MAP Kinase Signaling System
dc.subject Male
dc.subject Mitogen-Activated Protein Kinases
dc.subject Molecular Sequence Data
dc.subject Neoplasm Proteins
dc.subject Phosphatidylinositol 3-Kinases
dc.subject Prostatic Neoplasms
dc.subject Protein Kinases
dc.subject Protein Structure, Tertiary
dc.subject Proto-Oncogene Proteins c-akt
dc.subject Signal Transduction
dc.subject Transcription, Genetic
dc.title Ligation of cell surface GRP78 with antibody directed against the COOH-terminal domain of GRP78 suppresses Ras/MAPK and PI 3-kinase/AKT signaling while promoting caspase activation in human prostate cancer cells.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US 2010-1-1 en_US
duke.description.endpage 152 en_US
duke.description.issue 2 en_US
duke.description.startpage 142 en_US
duke.description.volume 9 en_US
dc.relation.journal Cancer Biology & Therapy en_US
pubs.issue 2
pubs.organisational-group /Duke
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pathology
pubs.publication-status Published
pubs.volume 9
dc.identifier.eissn 1555-8576

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