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PLoS One. 2014 Jun 26;9(6):e100896. doi: 10.1371/journal.pone.0100896. eCollection 2014.

Glycerol-3-phosphate acyltranferase-2 behaves as a cancer testis gene and promotes growth and tumorigenicity of the breast cancer MDA-MB-231 cell line.

Author information

1
Instituto de Investigaciones Bioquímicas de La Plata, Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Médicas, Universidad Nacional de La Plata. La Plata, Argentina.
2
Centro de Investigaciones Inmunológicas Básicas y Aplicadas, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina.
3
Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina, United States of America.

Abstract

The de novo synthesis of glycerolipids in mammalian cells begins with the acylation of glycerol-3-phosphate, catalyzed by glycerol-3-phosphate acyltransferase (GPAT). GPAT2 is a mitochondrial isoform primarily expressed in testis under physiological conditions. Because it is aberrantly expressed in multiple myeloma, it has been proposed as a novel cancer testis gene. Using a bioinformatics approach, we found that GPAT2 is highly expressed in melanoma, lung, prostate and breast cancer, and we validated GPAT2 expression at the protein level in breast cancer by immunohistochemistry. In this case GPAT2 expression correlated with a higher histological grade. 5-Aza-2' deoxycytidine treatment of human cells lines induced GPAT2 expression suggesting epigenetic regulation of gene expression. In order to evaluate the contribution of GPAT2 to the tumor phenotype, we silenced its expression in MDA-MB-231 cells. GPAT2 knockdown diminished cell proliferation, anchorage independent growth, migration and tumorigenicity, and increased staurosporine-induced apoptosis. In contrast, GPAT2 over-expression increased cell proliferation rate and resistance to staurosporine-induced apoptosis. To understand the functional role of GPAT2, we performed a co-expression analysis in mouse and human testis and found a significant association with semantic terms involved in cell cycle, DNA integrity maintenance, piRNA biogenesis and epigenetic regulation. Overall, these results indicate the GPAT2 would be directly associated with the control of cell proliferation. In conclusion, we confirm GPAT2 as a cancer testis gene and that its expression contributes to the tumor phenotype of MDA-MB-231 cells.

PMID:
24967918
PMCID:
PMC4072688
DOI:
10.1371/journal.pone.0100896
[Indexed for MEDLINE]
Free PMC Article

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