Glycoproteins in Claudin-Low Breast Cancer Cell Lines Have a Unique Expression Profile - PubMed (original) (raw)

Glycoproteins in Claudin-Low Breast Cancer Cell Lines Have a Unique Expression Profile

Ten-Yang Yen et al. J Proteome Res. 2017.

Abstract

Claudin proteins are components of epithelial tight junctions; a subtype of breast cancer has been defined by the reduced expression of mRNA for claudins and other genes. Here, we characterize the expression of glycoproteins in breast cell lines for the claudin-low subtype using liquid chromatography/tandem mass spectrometry. Unsupervised clustering techniques reveal a group of claudin-low cell lines that is distinct from nonmalignant, basal, and luminal lines. The claudin-low cell lines express F11R, EPCAM, and other proteins at very low levels, whereas CD44 is expressed at a high level. Comparison of mRNA expression to glycoprotein expression shows modest correlation; the best agreement occurs when the mRNA expression level is lowest and little or no protein is detected. These findings from cell lines are compared to those for tumor samples by the Clinical Proteomic Tumor Analysis Consortium (CPTAC). The CPTAC samples contain a group low in CLDN3. The samples low in CLDN3 proteins share many differentially expressed glycoproteins with the claudin-low cell lines. In contrast to the situation for cell lines or patient samples classified as claudin-low by RNA expression, however, most of the tumor samples low in CLDN3 protein express the estrogen receptor or HER2. These tumor samples express CD44 protein at low rather than high levels. There is no correlation between CLDN3 gene expression and protein expression in these CPTAC samples; hence, the claudin-low subtype defined by gene expression is not the same group of tumors as that defined by low expression of CLDN3 protein.

Keywords: breast cancer; cell lines; claudin; glycoprotein; mass spectrometry; supervised classification.

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Conflict of interest statement

Notes

The authors declare no competing financial interest.

Figures

Figure 1

Figure 1

Hierarchical clustering analysis of the 26 breast cancer cell lines. Color key: nonmalignant, green; claudin-low, violet; basal, blue; luminal, red.

Figure 2

Figure 2

Principal components analysis of the cell lines. (a) Analysis using all 399 glycoproteins. The decision boundary separates the claudin-low cell lines from the others. (b) Principal components analysis using a random set of 50 glycoproteins. Color key: nonmalignant, green; basal, blue (HCC38 is the triangle, HCC1395 the diamond); claudin-low, violet; luminal, red. The asterisks correspond to cell lines that over-express HER2.

Figure 3

Figure 3

Frequency distribution for two-sample t statistics. The curve is the sum of two normal distributions with means of −1.63 and 0.82 and standard deviations of 0.77 and 0.61.

Figure 4

Figure 4

Relation between changes in expression of mRNA and glycoproteins. (a) Scatterplot of t statistics for mRNA and the claudin-low glycoproteins identified in this study. There are 391 proteins for which both mRNA and glycoprotein data are available. (b) Scatterplot of scores (logarithms of fold change) for differentially expressed mRNA from the nine cell line claudin-low predictor data set (Supplemental Data from Prat et al.) and t statistics for glycoproteins. There are 61 genes for which both mRNA and glycoprotein data are available.

Figure 5

Figure 5

Claudins and CD44 in a breast tumor data set (CPTAC). (a) Frequency distribution of CLDN3 and CLDN7 expression. The tail of 18 samples on the left of the CLDN3 data was used to identify the claudin-low samples. (b) Principal components plot. The claudin-low samples are identified by the violet symbols. (c) Association between CLDN3 and CD44.

Figure 6

Figure 6

Association between mRNA expression and protein expression for CLDN3 in the CPTAC data. The samples low in CLDN3 protein are identified by violet symbols.

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