Metabolomic Profiling Reveals a Role for Androgen in Activating Amino Acid Metabolism and Methylation in Prostate Cancer Cells

Hdl Handle:
http://hdl.handle.net/10675.2/666
Title:
Metabolomic Profiling Reveals a Role for Androgen in Activating Amino Acid Metabolism and Methylation in Prostate Cancer Cells
Authors:
Putluri, Nagireddy; Shojaie, Ali; Vasu, Vihas T.; Nalluri, Srilatha; Vareed, Shaiju K.; Putluri, Vasanta; Vivekanandan-Giri, Anuradha; Byun, Jeman; Pennathur, Subramaniam; Sana, Theodore R.; Fischer, Steven M.; Palapattu, Ganesh S.; Creighton, Chad J.; Michailidis, George; Sreekumar, Arun
Abstract:
Prostate cancer is the second leading cause of cancer related death in American men. Development and progression of clinically localized prostate cancer is highly dependent on androgen signaling. Metastatic tumors are initially responsive to anti-androgen therapy, however become resistant to this regimen upon progression. Genomic and proteomic studies have implicated a role for androgen in regulating metabolic processes in prostate cancer. However, there have been no metabolomic profiling studies conducted thus far that have examined androgen-regulated biochemical processes in prostate cancer. Here, we have used unbiased metabolomic profiling coupled with enrichment-based bioprocess mapping to obtain insights into the biochemical alterations mediated by androgen in prostate cancer cell lines. Our findings indicate that androgen exposure results in elevation of amino acid metabolism and alteration of methylation potential in prostate cancer cells. Further, metabolic phenotyping studies confirm higher flux through pathways associated with amino acid metabolism in prostate cancer cells treated with androgen. These findings provide insight into the potential biochemical processes regulated by androgen signaling in prostate cancer. Clinically, if validated, these pathways could be exploited to develop therapeutic strategies that supplement current androgen ablative treatments while the observed androgen-regulated metabolic signatures could be employed as biomarkers that presage the development of castrate-resistant prostate cancer.
Citation:
PLoS One. 2011 Jul 18; 6(7):e21417
Issue Date:
18-Jul-2011
URI:
http://hdl.handle.net/10675.2/666
DOI:
10.1371/journal.pone.0021417
PubMed ID:
21789170
PubMed Central ID:
PMC3138744
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Georgia Cancer Center: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorPutluri, Nagireddyen_US
dc.contributor.authorShojaie, Alien_US
dc.contributor.authorVasu, Vihas T.en_US
dc.contributor.authorNalluri, Srilathaen_US
dc.contributor.authorVareed, Shaiju K.en_US
dc.contributor.authorPutluri, Vasantaen_US
dc.contributor.authorVivekanandan-Giri, Anuradhaen_US
dc.contributor.authorByun, Jemanen_US
dc.contributor.authorPennathur, Subramaniamen_US
dc.contributor.authorSana, Theodore R.en_US
dc.contributor.authorFischer, Steven M.en_US
dc.contributor.authorPalapattu, Ganesh S.en_US
dc.contributor.authorCreighton, Chad J.en_US
dc.contributor.authorMichailidis, Georgeen_US
dc.contributor.authorSreekumar, Arunen_US
dc.date.accessioned2012-10-26T16:27:01Z-
dc.date.available2012-10-26T16:27:01Z-
dc.date.issued2011-07-18en_US
dc.identifier.citationPLoS One. 2011 Jul 18; 6(7):e21417en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid21789170en_US
dc.identifier.doi10.1371/journal.pone.0021417en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/666-
dc.description.abstractProstate cancer is the second leading cause of cancer related death in American men. Development and progression of clinically localized prostate cancer is highly dependent on androgen signaling. Metastatic tumors are initially responsive to anti-androgen therapy, however become resistant to this regimen upon progression. Genomic and proteomic studies have implicated a role for androgen in regulating metabolic processes in prostate cancer. However, there have been no metabolomic profiling studies conducted thus far that have examined androgen-regulated biochemical processes in prostate cancer. Here, we have used unbiased metabolomic profiling coupled with enrichment-based bioprocess mapping to obtain insights into the biochemical alterations mediated by androgen in prostate cancer cell lines. Our findings indicate that androgen exposure results in elevation of amino acid metabolism and alteration of methylation potential in prostate cancer cells. Further, metabolic phenotyping studies confirm higher flux through pathways associated with amino acid metabolism in prostate cancer cells treated with androgen. These findings provide insight into the potential biochemical processes regulated by androgen signaling in prostate cancer. Clinically, if validated, these pathways could be exploited to develop therapeutic strategies that supplement current androgen ablative treatments while the observed androgen-regulated metabolic signatures could be employed as biomarkers that presage the development of castrate-resistant prostate cancer.en_US
dc.rightsPutluri et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectMedicineen_US
dc.subjectOncologyen_US
dc.subjectCancers and Neoplasmsen_US
dc.subjectGenitourinary Tract Tumorsen_US
dc.subjectProstate Canceren_US
dc.subjectUrologyen_US
dc.subjectProstate Diseasesen_US
dc.subjectProstate Canceren_US
dc.subjectGenitourinary Cancersen_US
dc.titleMetabolomic Profiling Reveals a Role for Androgen in Activating Amino Acid Metabolism and Methylation in Prostate Cancer Cellsen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3138744en_US
dc.contributor.corporatenameGHSU Cancer Center-
dc.contributor.corporatenameDepartment of Biochemistry and Molecular Biology-
dc.contributor.corporatenameDepartment of Surgery-

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