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Differential Expression of Enzymes Associated with Serine/Glycine Metabolism in Different Breast Cancer Subtypes

Authors
 Sang Kyum Kim  ;  Woo Hee Jung  ;  Ja Seung Koo 
Citation
 PLOS ONE, Vol.9(6) : e101004, 2014 
Journal Title
 PLOS ONE 
Issue Date
2014
MeSH
Blotting, Western ; Breast Neoplasms/classification* ; Breast Neoplasms/enzymology* ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Disease-Free Survival ; Female ; Glycine/metabolism* ; Glycolysis ; Humans ; Middle Aged ; Multivariate Analysis ; Neoplasm Proteins/metabolism ; Phenotype ; Serine/metabolism*
Abstract
PURPOSE: Glycine and serine are well-known, classic metabolites of glycolysis. Here, we profiled the expression of enzymes associated with serine/glycine metabolism in different molecular subtypes of breast cancer and discuss their potential clinical implications. METHODS: We used western blotting and immunohistochemistry to examine five serine-/glycine-metabolism-associated proteins (PHGDH, PSAT, PSPH, SHMT, and GLDC) in six breast cancer cell lines and 709 breast cancer cases using tissue microarray (TMA). RESULTS: PHGDH and PSPH, associated with serine metabolism, were highly expressed in the TNBC cells. GLDC, associated with glycine metabolism, was highly expressed in HER-2-positive MDA-MB-453 and TNBC-related MDA-MB-435S. TMA showed that the TNBC-type breast cancer tissues highly expressed PHGDH, PSPH, and SHMT1, but not the luminal-A-type tissues (p<0.001). PSPH and SHMT1 expression in the tumor stroma of HER-2-type cancers was the highest, but the luminal-A tissues showed the lowest expression (p<0.001). GLDC was most frequently expressed in cancer cells and stroma of the HER-2-positive cancers and least frequently in TNBC (p<0.001). By Cox multivariate analysis, tumor PSPH positivity (hazard ratio [HR]: 2.068, 95% confidence interval [CI]: 1.049-4.079, p = 0.036), stromal PSPH positivity (HR: 2.152, 95% CI: 1.107-4.184, p = 0.024), and stromal SHMT1 negativity (HR: 2.142, 95% CI: 1.219-3.764, p = 0.008) were associated with short overall survival. CONCLUSIONS: Expression of serine-metabolism-associated proteins was increased in TNBC and decreased in the luminal-A cancers. Expression of glycine-metabolism-associated proteins was high in the tumor and stroma of HER-2-positive cancers.
Files in This Item:
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DOI
10.1371/journal.pone.0101004
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Koo, Ja Seung(구자승) ORCID logo https://orcid.org/0000-0003-4546-4709
Kim, Sang Kyum(김상겸) ORCID logo https://orcid.org/0000-0003-0768-9923
Jung, Woo Hee(정우희)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/98967
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