|Cancer||Cell death||Cell cycle||Cytoskeleton||Exo/endocytosis||Differentiation||Division||Organelles||Signalling||Stem cells||Trafficking|
Cell Biology International (2010) 34, S5 (Printed in Great Britain)
Molecular mechanism of the dysregulated TERE1/UBIAD1 in bladder carcinoma
Yanzhi Xia12, Bo Wang3, Xiong Wei1, Wei Zhao1, Ximing Wang2 and Ling Hong1
1Key Laboratory of Molecular Biophysics, Ministry of Education, College of Life Science and Technology, 2Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Hubei, P.R. China, and 3Hubei Center of Medical Genetics, Hubei Maternity and Child Health Hospital, Hubei, P.R. China
Down-regulation of TERE1/UBIAD1 (TERE1, transitional epithelial response gene) causes multiple human cancers including bladder carcinoma. TERE1 also contributes to SCCD (Schnyder crystalline corneal dystrophy). Although the role of TERE1/UBIAD1 in lipid metabolism gradually becomes clear, its function in tumor suppression remains to be clarified. The mRNA and protein level of both TERE1/UBIAD1 and hTERT was analyzed by RT-PCR and western blotting in normal and carcinoma bladder tissues. TERE1 siRNA oligos was exploited to knock down the expression level of TERE1 in Human Urothelial Cells (HUC), hTERT expression level and the ERK phosphorylation level were measured. Our results showed that the decrease of TERE1 expression was closely related to the increase of hTERT expression and ERK phosphorylation in transitional cell carcinoma (TCC) samples. hTERT level and ERK phosphorylation in TERE1 knock down cell line increased with the subsequent cell proliferation. Adding the MEK inhibitor U0126 into the above transfected HUC inhibited the ERK phosphorylation and hTERT transcription. In conclusion, our result is the initial demonstration that down-regulation of TERE1 activated MAPK signaling pathway and induced subsequent bladder cell proliferation. TERE1 might be a new negative regulator of the MAPK signaling pathway which plays a pivotal role in the development of bladder carcinoma.
Published online 1 August 2010, doi:10.1042/CBI034S005c
© The Author(s) Journal compilation © 2010 Portland Press Limited