Regulation of hTERT transcription: a target of cellular and viral mechanisms for immortalization and carcinogenesis.
A hallmark of human cancer cells is immortal cell growth, which is associated with telomere maintenance by telomerase. The transcriptional regulation of the human telomerase reverse transcriptase (hTERT) gene is a major mechanism that negatively and positively controls telomerase activity in normal and cancer cells, respectively. A growing body of data suggests that various cellular and viral factors and pathways involved in cell senescence, immortalization and carcinogenesis act on the hTERT promoter. The activity of the hTERT promoter is regulated, either directly or through signaling pathways, by oncogene products (e.g., Myc and Ets families) and tumor suppressor proteins (e.g., BRCA1). Endogenous factors involved in the physiological repression of the hTERT gene have also been revealed by chromosome transfer experiments. The integration of viral genomes in the hTERT locus can lead to hTERT activation and telomerase induction. Here, we summarize these findings and pay special attention to recent findings with relevance to the endogenous regulatory mechanisms of hTERT transcription.
Horikawa
Izumi
I
Laboratory of Biosystems and Cancer, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 5046, Bethesda, MD, 20892, USA, horikawi@mail.nih.gov.
Michishita
Eriko
E
Barrett
J Carl
JC