Abstract
GRP78/BiP has recently emerged as a novel biomarker for aggressive prostate cancer. Here, we report that homozygous deletion of Grp78 specifically in mouse prostate epithelium suppresses prostate tumorigenesis without affecting postnatal prostate development and growth. Mouse prostates with double conditional knockout of Grp78 and Pten exhibit normal histology and cytology, in contrast to the invasive adenocarcinoma in mouse prostates with Pten inactivation. AKT activation in Pten null prostate epithelium is inhibited by Grp78 homozygous deletion, corresponding with suppression of AKT phosphorylation by GRP78 knockdown in prostate cancer cell line. Thus, inactivation of GRP78 may represent a previously undescribed approach to stop prostate cancer and potentially other cancers resulting from the loss of PTEN tumor suppression and/or activation of the oncogenic AKT.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adenocarcinoma / metabolism*
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Adenocarcinoma / pathology
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Adenocarcinoma / physiopathology
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Animals
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Endoplasmic Reticulum Chaperone BiP
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Epithelium / pathology
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Epithelium / physiology
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Fluorescent Antibody Technique
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Gene Expression Regulation, Neoplastic
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Heat-Shock Proteins / genetics*
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Heat-Shock Proteins / metabolism
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Homozygote
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Molecular Chaperones / genetics*
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Molecular Chaperones / metabolism
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PTEN Phosphohydrolase / genetics
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PTEN Phosphohydrolase / metabolism*
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Prostate / growth & development
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Prostate / pathology
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Prostate / physiology
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Prostatic Neoplasms / metabolism*
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Prostatic Neoplasms / pathology
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Prostatic Neoplasms / physiopathology
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Proto-Oncogene Proteins c-akt / metabolism*
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Signal Transduction / physiology*
Substances
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Endoplasmic Reticulum Chaperone BiP
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Heat-Shock Proteins
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Hspa5 protein, mouse
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Molecular Chaperones
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Proto-Oncogene Proteins c-akt
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PTEN Phosphohydrolase
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Pten protein, mouse