Glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) expression correlates with malignant choline phospholipid metabolite profiles in human breast cancer

Maria D. Cao, Mailin Döpkens, Balaji Krishnamachary, Farhad Vesuna, Mayur M. Gadiya, Per E. Lønning, Zaver M Bhujwalla, Ingrid S. Gribbestad, Kristine Glunde

Research output: Contribution to journalArticle

Abstract

Altered choline phospholipid metabolism is a hallmark of cancer, leading to malignant choline metabolite profiles consisting of low glycerophosphocholine (GPC) and high phosphocholine (PC) in human breast cancers. Glycerophosphocholine phosphodiesterase (GPC-PDE) catalyzes the degradation of GPC to free choline and glycerol-3-phosphate. The gene(s) encoding for the GPC-PDE(s) responsible for GPC degradation in breast cancers have not yet been identified. Here, we demonstrate for the first time that the GPC-PDE encoded by glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) is associated with breast cancer malignancy. Two human breast cancer cell lines (n=8 and n=10) and primary human breast tumor samples (n=19) were studied with combined MRS and quantitative reverse transcription-polymerase chain reaction to investigate several isoforms of GDPD expression with respect to choline phospholipid metabolite levels. Of the five GDPDs tested, GDPD5 was found to be significantly overexpressed in highly malignant estrogen receptor negative (ER-) compared with weakly malignant estrogen receptor positive (ER+) human breast cancer cells (p=0.027) and breast tumors from patients (p=0.015). GDPD5 showed significantly positive correlations with PC (p- tumors in our patient cohort. Our study identified GDPD5 as a GPC-PDE that probably participates in the regulation of choline phospholipid metabolism in breast cancer, which possibly occurs in cooperation with CHKA and PLD1.

Original languageEnglish (US)
Pages (from-to)1033-1042
Number of pages10
JournalNMR in Biomedicine
Volume25
Issue number9
DOIs
StatePublished - Sep 2012

Fingerprint

Metabolites
Choline
Phospholipids
Breast Neoplasms
Tumors
Phosphorylcholine
Metabolism
Estrogen Receptors
Cells
Degradation
Gene encoding
Polymerase chain reaction
Transcription
Protein Isoforms
Neoplasms
glycerophosphodiester phosphodiesterase
Reverse Transcription
Cell Line
Polymerase Chain Reaction
Genes

Keywords

  • Breast cancer
  • Choline kinase
  • Choline phospholipid metabolism
  • Glycerophosphodiester phosphodiesterase domain containing 5
  • MRS

ASJC Scopus subject areas

  • Spectroscopy
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

Glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) expression correlates with malignant choline phospholipid metabolite profiles in human breast cancer. / Cao, Maria D.; Döpkens, Mailin; Krishnamachary, Balaji; Vesuna, Farhad; Gadiya, Mayur M.; Lønning, Per E.; Bhujwalla, Zaver M; Gribbestad, Ingrid S.; Glunde, Kristine.

In: NMR in Biomedicine, Vol. 25, No. 9, 09.2012, p. 1033-1042.

Research output: Contribution to journalArticle

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