1.Glycogen synthase kinase3 and prostate cancer: An update.
Qing-Ting HU ; Chang-Bai LIU ; Ben-Yi LI
National Journal of Andrology 2017;23(2):178-182
Glycogen synthase kinase3 (GSK3α and GSK3β) are serine/threonine protein kinases acting on numerous substrates and involved in the regulation of various cellular functions such as their proliferation, survival, glycogen metabolism, and autophagy. Accumulating evidence indicates that the expression of GSK3α is increased mainly in androgendependent while that of GSK3β in androgenindependent prostate cancer, and that GSK3β is also involved in the regulation of the transactivation of the androgen receptor (AR) and growth of prostate cancer. Animal experiments have proved that some GSK3 inhibitors, such as lithium, can significantly suppress tumor growth in different animal models of prostate cancer. The GSK3 inhibitor is promising to be an important agent for the clinical management of prostate cancer.
Androgens
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Animals
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Cell Line, Tumor
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Glycogen Synthase Kinase 3
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antagonists & inhibitors
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metabolism
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Glycogen Synthase Kinase 3 beta
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antagonists & inhibitors
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metabolism
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Humans
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Male
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Neoplasm Proteins
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metabolism
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Neoplasms, Hormone-Dependent
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enzymology
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metabolism
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Prostatic Neoplasms
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drug therapy
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enzymology
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pathology
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Receptors, Androgen
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metabolism
2.Expression of procaspase 3 and activated caspase 3 and its relevance in hormone-responsive gallbladder carcinoma chemotherapy.
Sanjeev Kumar MAURYA ; Mallika TEWARI ; Bechan SHARMA ; Hari Shanker SHUKLA
The Korean Journal of Internal Medicine 2013;28(5):573-578
BACKGROUND/AIMS: The higher incidence of gallbladder cancer (GBC) in females has been accredited to the involvement of hormones. The clinical implications of sex hormone receptors in GBC are well established. Cysteine proteases (such as caspase-3-9, etc.) are known to play a central role in the apoptotic pathway. Of these, the downstream enzyme caspase-3 is often activated in the apoptotic pathway. The aim of this work was to examine the status of apoptosis (which directly correlated with the level of active caspase-3) in hormone-responsive GBC. METHODS: We used 10 androgen receptor (AR)-positive, 14 estrogen receptor (ER)-positive, 12 HER/neu-positive, eight triple positive, and 10 triple negative malignant GBC human tissue samples. We isolated the total cellular protein from tumor tissues and carried out Western blotting using antipro-caspase-3 and anti-activated caspase-3 antibodies. RESULTS: ER and HER/neu-positive GBC exhibited high caspase-3 activity and low procaspase-3 activity, whereas AR-positive GBC showed no significant level of apoptosis. We also evaluated the apoptosis status of triple positive GBC and triple negative GBC, and found significant apoptosis in triple positive GBC. CONCLUSIONS: The results indicate that ER and HER/neu-positive GBCs had active apoptosis, whereas AR-positive GBC was highly resistant to apoptosis.
Antineoplastic Agents, Hormonal/therapeutic use
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*Apoptosis/drug effects
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Blotting, Western
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Carcinoma/drug therapy/*enzymology/pathology
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Caspase 3/*analysis
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Drug Resistance, Neoplasm
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Enzyme Activation
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Gallbladder Neoplasms/drug therapy/*enzymology/pathology
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Humans
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Neoplasms, Hormone-Dependent/drug therapy/*enzymology/pathology
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Receptor, erbB-2/analysis
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Receptors, Androgen/analysis
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Receptors, Estrogen/analysis
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Tumor Markers, Biological/*analysis