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DTIC ADA561161: A Novel Anti-Beta2-Microglobulin Antibody Inhibitio... |
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by Defense Technical Information Center |
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Beta 2-microglobulin ( 2M) is a signaling and growth- |
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promoting factor stimulating prostate cancer cell |
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proliferation and progression. Blockade of the Beta 2M |
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signaling axis resulted in the inhibition of androgen |
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receptor (AR) and its target gene, prostate-specific |
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antigen (PSA), and the induction of programmed death of |
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prostate cancer cells in vitro and in vivo. Also, we |
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identified a new cis-acting element, sterol regulatory |
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element-binding protein-1 (SREBP-1) binding site, within |
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the 5 -flanking human AR promoter region and its binding |
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transcription factor, SREBP-1, regulating AR |
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transcription by anti- Beta 2M monoclonal antibody in |
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prostate cancer cells. Furthermore, we revealed the novel |
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molecular mechanism by which SREBP-1 promotes prostate |
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cancer growth and progression. Alteration of SREBP-1 |
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expression leads to regulate AR expression, cell growth, |
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migration and invasion in prostate cancer cells. SREBP-1 |
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also showed to induce fatty acid and lipid formation in |
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prostate cancer cells through increase of fatty acid |
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synthase expression. Additionally, SREBP-1 induced |
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oxidative stress and NADPH oxidase 5 (Nox5) expression in |
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prostate cancer cells. In subcutaneous xenograft mouse |
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models, SREBP-1 significantly increased LNCaP tumor |
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growth and promoted prostate tumor castration-resistant |
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progression. These findings provided a new concept to |
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reveal the role of Beta 2M and its related signaling |
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pathways, including AR, SREBP-1, fat metabolism and |
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oxidative stress, contribute to prostate cancer growth, |
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survival and progression, and further provides a new |
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potential target to prevent and treat prostate cancer |
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malignancy by using anti-Beta 2M monoclonal antibody. |
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Date Published: 2018-09-02 07:12:07 |
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Identifier: DTIC_ADA561161 |
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Item Size: 33583479 |
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Language: english |
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Media Type: texts |
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# Topics |
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DTIC Archive; ; CEDARS-SINAI MEDICAL ... |
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@chris85 |
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