hTERT regulation mechanism by cancer-specific transactivators

Abstract

Backgrounds;Telomere length is maintained by the telomerase which is a ribonucleoprotein polymerase. In normal human cells, telomere length is not maintained and telomerase is not active except sperm and stem cells. However, in tumors, telomerase becomes active. Telomere length is a molecular clock determining cellular fate toward apoptosis, senescence or immortalization. So telomerase, as a key factor for telomere length has been studied to figure out its control mechanism. Human telomerase catalytic subunit(hTERT), as a component of telomerase was identified as a determining factor of telomerase activity. Methods; 5` end of hTERT cDNA was determined by 5`RACE and hTERT promoter was cloned by genomic PCR. Several deletion constructs for hTERT promoter were generated. Transient transfection and Firefly luciferase assay were done with hTERT promoter and transcription factor was cloned from fetal cDNA library and screened for hTERT promoter. Results; Several transcription factors including MAZ, Myc, E1AF and others were cloned. Those factors were proved to have variable transcriptional activity for hTERT according to cellular context. Conclusion; hTERT transcription must be activated during carcinogenesis and several transcription factors seemed to be involved in its activation. Those factors can be specific to cancer cells. However, any single factor cannot be the determinant for hTERT activation even though it can bind to hTERT promoter region. The interaction between several factors might be the determinant for hTERT activation of cancer cells.