Human telomerase reverse transcriptase (hTERT) is a target gene of β-catenin in human colorectal tumors.
The majority of colorectal cancers (CRCs) are characterized by a dysregulated canonical Wnt-signaling pathway leading to the stabilization and subsequent cellular increase and accumulation of β-catenin. After translocation into the nucleus, it acts as a transcription factor resulting in the expression of β-catenin target genes. These resemble most of the hallmarks of cancer except eternal life. The central mediator of this hallmark is hTERT (human telomerase reverse transcriptase). The hTERT gene is regulated, besides others, by the transcription factor c-Myc and, thus, indirectly via β-catenin as c-Myc is a β-catenin target gene. Interestingly, the expression patterns of hTERT and β-catenin, but not c-Myc are overlapping, probably because c-Myc is not only regulated by β-catenin, but also by many other transcription factors and pathways. Therefore, we argued that hTERT might be a direct target gene of β-catenin. In this study, we show evidence that β-catenin directly regulates the expression of the hTERT gene.
Pathologisches Institut der Ludwig-Maximilians-Universität, München, Germany. stefanie.jaitner@med.uni-muenchen.de
Stefanie
S
Jaitner
Jana A
JA
Reiche
Achim J
AJ
Schäffauer
Elke
E
Hiendlmeyer
Hermann
H
Herbst
Thomas
T
Brabletz
Thomas
T
Kirchner
Andreas
A
Jung
D047369:Chromatin Immunoprecipitation; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D024202:Electrophoretic Mobility Shift Assay; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D009841:Oligonucleotides / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism* / Q000627:therapeutic use
C489427:MYC protein, human; D009841:Oligonucleotides; D016271:Proto-Oncogene Proteins c-myc; D051176:beta Catenin; D019098:Telomerase