دورية أكاديمية
Survival advantage of AMPK activation to androgen-independent prostate cancer cells during energy stress
| العنوان: | Survival advantage of AMPK activation to androgen-independent prostate cancer cells during energy stress |
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| المؤلفون: | Chhipa, Rishi Raj, Wu, Yue, Mohler, James L., Ip, Clement |
| المصدر: | Cellular Signalling, 22(10) |
| سنة النشر: | 2010 |
| المجموعة: | Carolina Digital Repository (UNC - University of North Carolina) |
| مصطلحات موضوعية: | PARPpoly ADP-ribose, acetyl coenzyme A carboxylase, amino acid deprivation, AMP-activated protein kinase, mammalian target of rapamycin, AMPKAMP-activated protein kinase, mTORmammalian target of rapamycin, AADamino acid deprivation, glucose deprivation, GDglucose deprivation, ACCacetyl coenzyme A carboxylase, lactate dehydrogenase, GADPHglyceraldehyde 3-phosphate dehydrogenase, dominant negative, Compound C, glyceraldehyde 3-phosphate dehydrogenase, DNdominant negative, Comp CCompound C, LDHlactate dehydrogenase |
| الوصف: | Androgen-independent prostate cancer usually develops as a relapse following androgen ablation therapy. Removing androgen systemically causes vascular degeneration and nutrient depletion of the prostate tumor tissue. The fact that the malignancy later evolves to androgen-independence suggests that some cancer cells are able to survive the challenge of energy/nutrient deprivation. AMP-activated protein kinase (AMPK) is an important manager of energy stress. The present study was designed to investigate the role of AMPK in contributing to the survival of the androgen-independent phenotype. Most of the experiments were carried out in the androgen-dependent LNCaP cells and the androgen-independent C4-2 cells. These two cell lines have the same genetic background, since the C4-2 line is derived from the LNCaP line. Glucose deprivation (GD) was instituted to model energy stress encountered by these cells. The key findings are as follows. First, the activation of AMPK by GD was much stronger in C4-2 cells than in LNCaP cells, and the robustness of AMPK activation was correlated favorably with cell viability. Second, the response of AMPK was specific to energy deficiency rather than to amino acid deficiency. The activation of AMPK by GD was functional, as demonstrated by appropriate phosphorylation changes of mTOR and mTOR downstream substrates. Third, blocking AMPK activation by chemical inhibitor or dominant negative AMPK led to increased apoptotic cell death. The observation that similar results were found in other androgen-independent prostate cancer cell lines, including CW22Rv1 abd VCaP, provided further assurance that AMPK is a facilitator on the road to androgen-independence of prostate cancer cells. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.17615/th3y-dj59Test; https://cdr.lib.unc.edu/downloads/c534fv92q?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/c534fv92qTest |
| DOI: | 10.17615/th3y-dj59 |
| الإتاحة: | https://doi.org/10.17615/th3y-dj59Test https://cdr.lib.unc.edu/downloads/c534fv92q?file=thumbnailTest https://cdr.lib.unc.edu/downloads/c534fv92qTest |
| حقوق: | http://rightsstatements.org/vocab/InC/1.0Test/ |
| رقم الانضمام: | edsbas.29EBC363 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17615/th3y-dj59 |
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