Differential expression of enzymes associated with serine/glycine metabolism in different breast cancer subtypes.
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 a...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4076239?pdf=render |
| _version_ | 1819263141815517184 |
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| author | Sang Kyum Kim Woo Hee Jung Ja Seung Koo |
| author_facet | Sang Kyum Kim Woo Hee Jung Ja Seung Koo |
| author_sort | Sang Kyum Kim |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T20:08:53Z |
| format | Article |
| id | doaj.art-ec5d9b6c24bf4f998cf3591cc4ead522 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T20:08:53Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ec5d9b6c24bf4f998cf3591cc4ead5222022-12-21T17:32:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0196e10100410.1371/journal.pone.0101004Differential expression of enzymes associated with serine/glycine metabolism in different breast cancer subtypes.Sang Kyum KimWoo Hee JungJa Seung KooPURPOSE: 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.http://europepmc.org/articles/PMC4076239?pdf=render |
| spellingShingle | Sang Kyum Kim Woo Hee Jung Ja Seung Koo Differential expression of enzymes associated with serine/glycine metabolism in different breast cancer subtypes. PLoS ONE |
| title | Differential expression of enzymes associated with serine/glycine metabolism in different breast cancer subtypes. |
| title_full | Differential expression of enzymes associated with serine/glycine metabolism in different breast cancer subtypes. |
| title_fullStr | Differential expression of enzymes associated with serine/glycine metabolism in different breast cancer subtypes. |
| title_full_unstemmed | Differential expression of enzymes associated with serine/glycine metabolism in different breast cancer subtypes. |
| title_short | Differential expression of enzymes associated with serine/glycine metabolism in different breast cancer subtypes. |
| title_sort | differential expression of enzymes associated with serine glycine metabolism in different breast cancer subtypes |
| url | http://europepmc.org/articles/PMC4076239?pdf=render |
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