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CEBP factors regulate TERT promoter activity in WAP-T mice during mammary carcinogenesis.
MedLine Citation:
PMID:  23023397     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Telomerase is activated in the majority of invasive breast cancers, but the time-point of telomerase activation during mammary carcinogenesis is not clear. We have recently presented a transgenic mouse model to study human TERT gene expression in vivo (hTERTp-lacZ). In the present study, hTERTp-lacZxWAP-T bi-transgenic mice were generated to analyze the mechanisms responsible for human and mouse TERT up-regulation during tumor progression in vivo. We found that telomerase activity and TERT expression were consistently up-regulated in SV40-induced invasive mammary tumors compared with normal and hyperplastic tissues and ductal carcinoma in situ (DCIS). Human and mouse TERT genes are regulated similarly in the breast tissue, involving the CEBP transcription factors. Loss of CEBP-α and induction of CEBP-β expression correlated well with the activation of TERT expression in mouse mammary tumors. Transfection of CEBP-α into human or murine cells resulted in TERT repression whereas knock-down of CEBP-α in primary human mammary epithelial cells resulted in reactivation of endogenous TERT expression and telomerase activity. Conversely, ectopic expression of CEBP-β activated endogenous TERT gene expression. Moreover, ChIP and EMSA experiments revealed binding of CEBP-α and CEBP-β to human TERT-promoter. This is the first evidence indicating that CEBP-α and CEBP-β are involved in TERT gene regulation during carcinogenesis. © 2012 Wiley-Liss, Inc.
Authors:
Mukesh Kumar; Britta Witt; Uwe Knippschild; Sylvia Koch; Jitendra K Meena; Christina Heinlein; Julia M Weise; Frauke Krepulat; Florian Kuchenbauer; Sebastian Iben; Karl-Lenhard Rudolph; Wolfgang Deppert; Cagatay Günes
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-1
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  -     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 UICC.
Affiliation:
Institute of Molecular Medicine and Max-Planck Research Group on Stem Cell Aging Albert-Einstein-Allee 11, 89081 Ulm, Germany; Heinrich-Pette-Institute, Leibniz-Institute for Experimental Virology, Martinistr. 52, 20251 Hamburg, Germany.
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