Joelle Makoukji, Mohamad Raad, Katia Genadry, Sally El-Sitt, Nadine J. Makhoul, Ehab Saad Aldin, Eden Nohra, Mark Jabbour, Ajanthah Sangaralingam, Claude Chelala, Robert H. Habib, Fouad Boulos, Arafat Tfayli, Rose-Mary Boustany
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 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.
Pharmacology, Toxicology and Pharmaceutical Science
1
4%
Other
2
8%
Unknown
11
44%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 November 2015.
All research outputs
#15,097,615
of 26,147,626 outputs
Outputs from Frontiers in oncology
#4,002
of 22,908 outputs
Outputs of similar age
#136,917
of 293,097 outputs
Outputs of similar age from Frontiers in oncology
#19
of 66 outputs
Altmetric has tracked 26,147,626 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
So far Altmetric has tracked 22,908 research outputs from this source. They receive a mean Attention Score of 3.1. This one has done well, scoring higher than 81% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 293,097 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.
We're also able to compare this research output to 66 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 71% of its contemporaries.
