Glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) expression correlates with malignant choline phospholipid metabolite profiles in human breast cancer.
Glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) expression correlates with malignant choline phospholipid metabolite profiles in human breast cancer.
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DOI：
10.1002/nbm.2766
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发表时间：
2012-09
影响因子：
2.9
通讯作者：
Glunde, Kristine
中科院分区：
文献类型：
--
作者：
Cao, Maria D.;Doepkens, Mailin;Krishnamachary, Balaji;Vesuna, Farhad;Gadiya, Mayur M.;Lonning, Per E.;Bhujwalla, Zaver M.;Gribbestad, Ingrid S.;Glunde, Kristine
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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 have demonstrated 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 10) and primary human breast tumor samples (n=19) were studied with combined magnetic resonance spectroscopy (MRS) and qRT-PCR to investigate several isoforms of GDPD expression with respect to choline phospholipid metabolite levels. Out of five GDPDs tested, GDPD5 was found to be significantly overexpressed in highly malignant estrogen receptor negative (ER−) compared to 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<0.001), total choline (tCho) (P=0.007) and PC/GPC (P<0.001) levels in human breast tumors. GDPD5 showed a trend towards negative correlation with GPC levels (P=0.130). Human breast cancers with malignant choline metabolite profiles consisting of low GPC and high PC levels highly co-expressed GDPD5, choline kinase alpha (CHKA), and phosphatidylcholine-specific phospholipase D1 (PLD1), while cancers containing high GPC and relatively low PC levels displayed low co-expression of GDPD5, CHKA, and PLD1. GDPD5, CHKA and PLD1 were significantly overexpressed in highly malignant ER− tumors in our patient cohort. Our study identified GDPD5 as a GPC-PDE that likely participates in regulating choline phospholipid metabolism in breast cancer, which possibly occurs in cooperation with CHKA and PLD1.
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影响因子：
6.4
作者：
Eliyahu, Galit;Kreizman, Tamar;Degani, Hadassa
通讯作者：
Degani, Hadassa
影响因子：
11.2
作者：
Krishnamachary B;Glunde K;Wildes F;Mori N;Takagi T;Raman V;Bhujwalla ZM
通讯作者：
Bhujwalla ZM
影响因子：
4.6
作者：
AuBuchon, J. P.;de Wildt-Eggen, J.;Dumont, L. J.
通讯作者：
Dumont, L. J.
影响因子：
8.8
作者：
Gozgit, J. M.;Pentecost, B. T.;Marconi, S. A.;Ricketts-Loriaux, R. S. J.;Otis, C. N.;Arcaro, K. F.
通讯作者：
Arcaro, K. F.
影响因子：
4.8
作者：
Corda, Daniela;Kudo, Takahiro;Mariggio, Stefania
通讯作者：
Mariggio, Stefania