How can I monitor the ppp activity (pentose phosphate pathway) within cancer cell lines?
is that convince if i test relative enzyme mRNA level?
Dear Simeng,
The following publication is a good example for a study to monitor the ppp activity (pentose phosphate pathway) within cancer cell lines:
Original Article
Subject Category: Cancer metabolism
Citation: Oncogenesis (2014) 3, e103; doi:10.1038/oncsis.2014.18
Published online 26 May 2014
Regulation of the pentose phosphate pathway by an androgen receptor–mTOR-mediated mechanism and its role in prostate cancer cell growth
OPEN
E Tsouko1, A S Khan1, M A White1, J J Han1, Y Shi1, F A Merchant2, M A Sharpe3, L Xin4,5,6 and D E Frigo1,7
1Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX, USA
2Department of Engineering Technology, University of Houston, Houston, TX, USA
3Department of Neurosurgery, Houston Methodist Research Institute, Houston, TX, USA
4Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA
5Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA
6Dan L. Duncan Cancer Center, Houston, TX, USA
7Center for Genomic Medicine, Houston Methodist Research Institute, Houston, TX, USA
Correspondence: Dr DE Frigo, Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, 3605 Cullen Blvd—Bldg 545, Houston, TX 77204. E-mail: [email protected]
Received 27 March 2014; Accepted 23 April 2014
Topof pageAbstract
Cancer cells display an increased demand for glucose. Therefore, identifying the specific aspects of glucose metabolism that are involved in the pathogenesis of cancer may uncover novel therapeutic nodes. Recently, there has been a renewed interest in the role of the pentose phosphate pathway in cancer. This metabolic pathway is advantageous for rapidly growing cells because it provides nucleotide precursors and helps regenerate the reducing agent NADPH, which can contribute to reactive oxygen species (ROS) scavenging. Correspondingly, clinical data suggest glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, is upregulated in prostate cancer. We hypothesized that androgen receptor (AR) signaling, which plays an essential role in the disease, mediated prostate cancer cell growth in part by increasing flux through the pentose phosphate pathway. Here, we determined that G6PD, NADPH and ribose synthesis were all increased by AR signaling. Further, this process was necessary to modulate ROS levels. Pharmacological or molecular inhibition of G6PD abolished these effects and blocked androgen-mediated cell growth. Mechanistically, regulation of G6PD via AR in both hormone-sensitive and castration-resistant models of prostate cancer was abolished following rapamycin treatment, indicating that AR increased flux through the pentose phosphate pathway by the mammalian target of rapamycin (mTOR)-mediated upregulation of G6PD. Accordingly, in two separate mouse models of Pten deletion/elevated mTOR signaling, Pb-Cre;Ptenf/f and K8-CreERT2;Ptenf/f, G6PD levels correlated with prostate cancer progression in vivo. Importantly, G6PD levels remained high during progression to castration-resistant prostate cancer. Taken together, our data suggest that AR signaling can promote prostate cancer through the upregulation of G6PD and therefore, the flux of sugars through the pentose phosphate pathway. Hence, these findings support a vital role for other metabolic pathways (that is, not glycolysis) in prostate cancer cell growth and maintenance.
http://www.nature.com/oncsis/journal/v3/n5/full/oncsis201418a.html
Hoping this will be helpful,
Rafik
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