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

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.