Breast cancer is the most common
cancer in women worldwide. Elucidation of underlying biology and molecular pathways is necessary for improving therapeutic options and clinical outcomes. CLN3
protein (CLN3p), deficient in neurodegenerative CLN3 disease is anti-apoptotic, and defects in the CLN3 gene cause accelerated apoptosis of neurons in CLN3 disease and up-regulation of
ceramide. Dysregulated apoptotic pathways are often implicated in the development of the oncogenic phenotype. Predictably, CLN3
mRNA expression and CLN3
protein were up-regulated in a number of human and murine
breast cancer-cell lines. Here, we determine CLN3 expression in non-
tumor vs.
tumor samples from fresh and
formalin-fixed/
paraffin-embedded (FFPE) breast tissue and analyze the association between CLN3 overexpression and different clinicopathological characteristics of
breast cancer patients. Additionally, gene expression of 28
enzymes involved in
sphingolipid metabolism was determined. CLN3
mRNA is overexpressed in
tumor vs. non-
tumor breast tissue from FFPE and fresh samples, as well as in mouse MCF7
breast cancer compared to MCF10A normal cells. Of the clinicopathological characteristics of
tumor grade, age, menopause status,
estrogen receptor,
progesterone receptor, and
human epidermal growth factor receptor 2 (HER2), only absence of HER2 expression correlated with CLN3 overexpression.
Sphingolipid genes for
ceramide synthases 2 and 6 (CerS2; CerS6), delta(4)-desaturase
sphingolipid 2 (DEGS2), and acidic
sphingomyelinase (SMPD1) displayed higher expression levels in
breast cancer vs. control tissue, whereas
ceramide galactosyltransferase (UGT8) was underexpressed in
breast cancer samples. CLN3 may be a novel molecular target for
cancer drug discovery with the goal of modulation of
ceramide pathways.