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Metabolomic profiling reveals a role for androgen in activating amino acid metabolism and methylation in prostate cancer cells.

Putluri N, Shojaie A, Vasu VT, Nalluri S, Vareed SK, Putluri V, Vivekanandan-Giri A, Byun J, Pennathur S, Sana TR, Fischer SM, Palapattu GS, Creighton CJ, Michailidis G, Sreekumar A - PLoS ONE (2011)

Bottom Line: Metastatic tumors are initially responsive to anti-androgen therapy, however become resistant to this regimen upon progression.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.

View Article: PubMed Central - PubMed

Affiliation: Cancer Center, Medical College of Georgia, Augusta, Georgia, United States of America.

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.

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Metabolome of prostate cancer cell lines.A) Heat map representation of hierarchical clustering of 1,553 metabolites across 5 prostate cell lines. Sample classes are indicated by the colored bars [benign = green, androgen non-responsive PCa (ARI): yellow and androgen responsive PCa (ARD): red bar]. Columns represent individual cell lines and rows refer to distinct metabolites. Shades of yellow represent elevation of a metabolite and shades of blue represent decrease of a metabolite relative to the median metabolite levels (see color scale). B) Venn diagram representing the distribution of 1,553 metabolites measured across benign (RWPE), ARI (DU145 and PC3) and ARD (LNCaP and VCaP) cell lines using liquid chromatography coupled mass spectrometry. C) same as in (A), but for 72 named compounds D) Dendrogram representing hierarchical clustering of the prostate-related cell lines described in B, using compounds with significant differential expression.
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pone-0021417-g002: Metabolome of prostate cancer cell lines.A) Heat map representation of hierarchical clustering of 1,553 metabolites across 5 prostate cell lines. Sample classes are indicated by the colored bars [benign = green, androgen non-responsive PCa (ARI): yellow and androgen responsive PCa (ARD): red bar]. Columns represent individual cell lines and rows refer to distinct metabolites. Shades of yellow represent elevation of a metabolite and shades of blue represent decrease of a metabolite relative to the median metabolite levels (see color scale). B) Venn diagram representing the distribution of 1,553 metabolites measured across benign (RWPE), ARI (DU145 and PC3) and ARD (LNCaP and VCaP) cell lines using liquid chromatography coupled mass spectrometry. C) same as in (A), but for 72 named compounds D) Dendrogram representing hierarchical clustering of the prostate-related cell lines described in B, using compounds with significant differential expression.

Mentions: A total of 1553 compounds were detected across the six prostate cell lines using the different mass spectrometry methods used in this study (see above, Figure 2A). Of these, 40 compounds were detected only in Ben while 102 and 55 compounds respectively were seen in ARI and ARD cell lines (Figure 2B). Notably, this compendium contained 72 named metabolites (Figure 2C). A hierarchical clustering profile based on compounds with significant differential expression perfectly delineates the prostate cell lines (Figure 2D).


Metabolomic profiling reveals a role for androgen in activating amino acid metabolism and methylation in prostate cancer cells.

Putluri N, Shojaie A, Vasu VT, Nalluri S, Vareed SK, Putluri V, Vivekanandan-Giri A, Byun J, Pennathur S, Sana TR, Fischer SM, Palapattu GS, Creighton CJ, Michailidis G, Sreekumar A - PLoS ONE (2011)

Metabolome of prostate cancer cell lines.A) Heat map representation of hierarchical clustering of 1,553 metabolites across 5 prostate cell lines. Sample classes are indicated by the colored bars [benign = green, androgen non-responsive PCa (ARI): yellow and androgen responsive PCa (ARD): red bar]. Columns represent individual cell lines and rows refer to distinct metabolites. Shades of yellow represent elevation of a metabolite and shades of blue represent decrease of a metabolite relative to the median metabolite levels (see color scale). B) Venn diagram representing the distribution of 1,553 metabolites measured across benign (RWPE), ARI (DU145 and PC3) and ARD (LNCaP and VCaP) cell lines using liquid chromatography coupled mass spectrometry. C) same as in (A), but for 72 named compounds D) Dendrogram representing hierarchical clustering of the prostate-related cell lines described in B, using compounds with significant differential expression.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3138744&req=5

pone-0021417-g002: Metabolome of prostate cancer cell lines.A) Heat map representation of hierarchical clustering of 1,553 metabolites across 5 prostate cell lines. Sample classes are indicated by the colored bars [benign = green, androgen non-responsive PCa (ARI): yellow and androgen responsive PCa (ARD): red bar]. Columns represent individual cell lines and rows refer to distinct metabolites. Shades of yellow represent elevation of a metabolite and shades of blue represent decrease of a metabolite relative to the median metabolite levels (see color scale). B) Venn diagram representing the distribution of 1,553 metabolites measured across benign (RWPE), ARI (DU145 and PC3) and ARD (LNCaP and VCaP) cell lines using liquid chromatography coupled mass spectrometry. C) same as in (A), but for 72 named compounds D) Dendrogram representing hierarchical clustering of the prostate-related cell lines described in B, using compounds with significant differential expression.
Mentions: A total of 1553 compounds were detected across the six prostate cell lines using the different mass spectrometry methods used in this study (see above, Figure 2A). Of these, 40 compounds were detected only in Ben while 102 and 55 compounds respectively were seen in ARI and ARD cell lines (Figure 2B). Notably, this compendium contained 72 named metabolites (Figure 2C). A hierarchical clustering profile based on compounds with significant differential expression perfectly delineates the prostate cell lines (Figure 2D).

Bottom Line: Metastatic tumors are initially responsive to anti-androgen therapy, however become resistant to this regimen upon progression.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.

View Article: PubMed Central - PubMed

Affiliation: Cancer Center, Medical College of Georgia, Augusta, Georgia, United States of America.

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.

Show MeSH
Related in: MedlinePlus