Juvenile Batten disease is a neurodegenerative disease caused by accelerated 
apoptotic death of photoreceptors and neurons attributable to defects in the 
CLN3 gene. CLN3 is antiapoptotic when overexpressed in NT2 neuronal precursor 
cells. CLN3 negatively modulates endogenous ceramide levels in NT2 cells and 
acts upstream of ceramide generation. Because defects in regulation of apoptosis 
are involved in the development of cancer, we evaluated the expression of CLN3 
on both mRNA and protein levels in a variety of cancer cell lines and solid 
colon cancer tissue. We also observed the effect of the blocking of CLN3 protein 
expression on cancer cell growth, survival, ceramide production, and apoptosis 
by using an adenovirus-bearing antisense CLN3 construct. We show that CLN3 mRNA 
and protein are overexpressed in glioblastoma (U-373G and T98g), neuroblastoma 
(IMR-32 and SK-N-MC), prostate (Du145, PC-3, and LNCaP), ovarian (SK-OV-3, 
SW626, and PA-1), breast (BT-20, BT-549, and BT-474), and colon (SW1116, SW480, 
and HCT 116) cancer cell lines but not in pancreatic (CAPAN and As-PC-1) or lung 
(A-549 and NCI-H520) cancer cell lines. CLN3 is also up-regulated in mouse 
melanoma and breast carcinoma cancer cell lines. We found CLN3 expression is 
22-330% higher than in corresponding normal colon control tissue in 8 of 10 
solid colon tumors. An adenovirus-expressing antisense CLN3 (Ad-AS-CLN3) blocks 
CLN3 protein expression in DU-145, BT-20, SW1116, and T98g cancer cell lines as 
seen by Western blot. Blocking of CLN3 expression using Ad-AS-CLN3 inhibits 
growth and viability of cancer cells. It also causes elevation in endogenous 
ceramide production through de novo ceramide synthesis and results in increased 
apoptosis as shown by propidium iodide and JC-1 staining. This suggests that 
Ad-AS-CLN3 may be an option for therapy in some cancers. More importantly these 
results suggest that CLN3 is a novel molecular target for cancer drug discovery.