association between cln3 (neuronal ceroid lipofuscinosis, cln3 type) gene expression and clinical characteristics of breast cancer patients
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ID: 193554
2015
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Abstract
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 upregulation of ceramide. Dysregulated apoptotic pathways are often implicated in the development of the oncogenic phenotype. Predictably, CLN3 mRNA expression and CLN3 protein were upregulated 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 (ER), progesterone receptor (PR), 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.
| Reference Key |
eboustany2015frontiersassociation
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| Authors | ;Rose-Mary eBoustany;Joelle eMakoukji;Mohamad eRaad;Katia eGenadry;Sally eEl-Sitt;Nadine J. Makhoul;Ehab eSaad Aldin;Eden eNohra;Mark eJabbour;Ajanthah eSangaralingam;Claude eChelala;Robert H. Habib;Fouad eBoulos;Arafat eTfayli |
| Journal | international journal of heat and technology |
| Year | 2015 |
| DOI |
10.3389/fonc.2015.00215
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| URL | |
| Keywords |
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