Metabolic profiling of transgenic adenocarcinoma of mouse prostate (TRAMP) Tissue by <sup>1</sup>H‐NMR analysis: evidence for unusual phospholipid metabolism

Teichert, Friederike; Verschoyle, Richard D.; Greaves, Peter; Edwards, Richard E.; Teahan, Orla; Jones, Donald J. L.; Wilson, Ian D.; Farmer, Peter B.; Steward, William P.; Gant, Timothy W.; Gescher, Andreas J.; Keun, Hector C.

doi:10.1002/pros.20761

Cited by 30 publications

(23 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Whether this occurs in prostate cancer requires further studies. Previous studies showed that PC was decreased in the plasma from patients with prostate cancer (18) and in prostate cancer tissues in a transgenic mouse model (19). In the study of lipid profiles in prostatic tissues, we found that all of the lysophosphatidylcholine (LPC) molecules, the preferable substrates of LPCAT1 (8–9), dramatically increased in prostate cancer tissues as compared to benign prostatic tissues, which makes the reaction catalyzed by LPCAT1 favorable towards the production of PC.…”

Section: Discussionmentioning

confidence: 97%

The expression level of lysophosphatidylcholine acyltransferase 1 (LPCAT1) correlates to the progression of prostate cancer

Zhou

Lawrence

et al. 2012

Experimental and Molecular Pathology

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 97%

The expression level of lysophosphatidylcholine acyltransferase 1 (LPCAT1) correlates to the progression of prostate cancer

Zhou

Lawrence

et al. 2012

Experimental and Molecular Pathology

View full text Add to dashboard Cite

“…NMR spectroscopy also represents another key tool for understanding the metabolic profiling of lipids, and lipid metabolites in intact tissues and in tissue extracts. Recently, this technique has been applied to the analysis of the relative metabolite peak areas of the glycerophosphoinositols in aqueous extracts and in intact tissues of normal prostate and prostate tumour tissues from C57BL/6J mice [135]. In mice with malignancy, significant decreases in the levels of GroPIns and glycerophosphocholine were reported.…”

Section: Methods Of Detectionmentioning

confidence: 99%

The glycerophosphoinositols: cellular metabolism and biological functions

Corda

Zizza

Varone

et al. 2009

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

The glycerophosphoinositols are cellular products of phospholipase A(2) and lysolipase activities on the membrane phosphoinositides. Their intracellular concentrations can vary upon oncogenic transformation, cell differentiation and hormonal stimulation. Specific glycerophosphodiester phosphodiesterases are involved in their catabolism, which, as with their formation, is under hormonal regulation. With their mechanisms of action including modulation of adenylyl cyclase, intracellular calcium levels, and Rho-GTPases, the glycerophosphoinositols have diverse effects in multiple cell types: induction of cell proliferation in thyroid cells; modulation of actin cytoskeleton organisation in fibroblasts; and reduction of the invasive potential of tumour cell lines. More recent investigations include their effects in inflammatory and immune responses. Indeed, the glycerophosphoinositols enhance cytokine-dependent chemotaxis in T-lymphocytes induced by SDF-1alpha-receptor activation, indicating roles for these compounds as modulators of T-cell signalling and T-cell responses.

show abstract

“…Also, human breast cancer cell lines show upregulation of ChoKα but not ChoKβ, when compared with normal mammary epithelial cells [21]. In that sense, it has been recently reported that in the prostate tumor mouse model (TRAMP), using IHQ immunodetection of ChoKβ, a low level expression of ChoKβ was found in tumoral samples compared with wild type tissues [31].…”

Section: Introductionmentioning

confidence: 98%

Differential Role of Human Choline Kinase α and β Enzymes in Lipid Metabolism: Implications in Cancer Onset and Treatment

et al. 2009

View full text Add to dashboard Cite

BackgroundThe Kennedy pathway generates phosphocoline and phosphoethanolamine through its two branches. Choline Kinase (ChoK) is the first enzyme of the Kennedy branch of synthesis of phosphocholine, the major component of the plasma membrane. ChoK family of proteins is composed by ChoKα and ChoKβ isoforms, the first one with two different variants of splicing. Recently ChoKα has been implicated in the carcinogenic process, since it is over-expressed in a variety of human cancers. However, no evidence for a role of ChoKβ in carcinogenesis has been reported.Methodology/Principal FindingsHere we compare the in vitro and in vivo properties of ChoKα1 and ChoKβ in lipid metabolism, and their potential role in carcinogenesis. Both ChoKα1 and ChoKβ showed choline and ethanolamine kinase activities when assayed in cell extracts, though with different affinity for their substrates. However, they behave differentially when overexpressed in whole cells. Whereas ChoKβ display an ethanolamine kinase role, ChoKα1 present a dual choline/ethanolamine kinase role, suggesting the involvement of each ChoK isoform in distinct biochemical pathways under in vivo conditions. In addition, while overexpression of ChoKα1 is oncogenic when overexpressed in HEK293T or MDCK cells, ChoKβ overexpression is not sufficient to induce in vitro cell transformation nor in vivo tumor growth. Furthermore, a significant upregulation of ChoKα1 mRNA levels in a panel of breast and lung cancer cell lines was found, but no changes in ChoKβ mRNA levels were observed. Finally, MN58b, a previously described potent inhibitor of ChoK with in vivo antitumoral activity, shows more than 20-fold higher efficiency towards ChoKα1 than ChoKβ.Conclusion/SignificanceThis study represents the first evidence of the distinct metabolic role of ChoKα and ChoKβ isoforms, suggesting different physiological roles and implications in human carcinogenesis. These findings constitute a step forward in the design of an antitumoral strategy based on ChoK inhibition.

show abstract

Metabolic profiling of transgenic adenocarcinoma of mouse prostate (TRAMP) Tissue by ¹H‐NMR analysis: evidence for unusual phospholipid metabolism

Abstract: Although prostate cancer in TRAMP mice shares some metabolic features with that in humans, it differs with respect to choline phospholipid metabolism, which could impact upon the interpretation of results from biomarker or chemotherapy/chemoprevention studies.

Cited by 30 publications

References 45 publications

The expression level of lysophosphatidylcholine acyltransferase 1 (LPCAT1) correlates to the progression of prostate cancer

The expression level of lysophosphatidylcholine acyltransferase 1 (LPCAT1) correlates to the progression of prostate cancer

The glycerophosphoinositols: cellular metabolism and biological functions

Differential Role of Human Choline Kinase α and β Enzymes in Lipid Metabolism: Implications in Cancer Onset and Treatment

Contact Info

Product

Resources

About

Metabolic profiling of transgenic adenocarcinoma of mouse prostate (TRAMP) Tissue by 1H‐NMR analysis: evidence for unusual phospholipid metabolism

Abstract: Although prostate cancer in TRAMP mice shares some metabolic features with that in humans, it differs with respect to choline phospholipid metabolism, which could impact upon the interpretation of results from biomarker or chemotherapy/chemoprevention studies.

Cited by 30 publications

References 45 publications

The expression level of lysophosphatidylcholine acyltransferase 1 (LPCAT1) correlates to the progression of prostate cancer

The expression level of lysophosphatidylcholine acyltransferase 1 (LPCAT1) correlates to the progression of prostate cancer

The glycerophosphoinositols: cellular metabolism and biological functions

Differential Role of Human Choline Kinase α and β Enzymes in Lipid Metabolism: Implications in Cancer Onset and Treatment

Contact Info

Product

Resources

About

Metabolic profiling of transgenic adenocarcinoma of mouse prostate (TRAMP) Tissue by ¹H‐NMR analysis: evidence for unusual phospholipid metabolism