Heregulin, a new regulator of telomere length in human cells

Oncotarget
Javier A MenendezRuth Lupu

Abstract

The growth factor heregulin (HRG) promotes breast cancer (BC) tumorigenesis and metastasis and differentially modulates BC cell responses to DNA-damaging agents via its dual extracellular and nuclear localization. Given the central role of telomere dysfunction to drive carcinogenesis and to alter the chemotherapeutic profile of transformed cells, we hypothesized that an unanticipated nuclear function of HRG might be to regulate telomere length. Engineered overexpression of the HRGβ2 isoform in non-aggressive, HRG-negative MCF-7 BC cells resulted in a significant shortening of telomeres (up to 1.3 kb) as measured by Southern blotting of telomere terminal restriction fragments. Conversely, antisense-mediated suppression of HRGβ2 in highly aggressive, HRG-overexpressing MDA-MB-231 and Hs578T cells increased telomere length up to 3.0 kb. HRGβ2 overexpression promoted a marked upregulation of telomere-binding protein 2 (TRF2) protein expression, whereas its knockdown profoundly decreased TRF2 expression. Double staining of endogenous HRGβ2 with telomere-specific peptide nucleic acid probe/fluorescence in situ hybridization (PNA/FISH) revealed the partial localization of HRG at the chromosome ends. Moreover, a predominantly nucleopla...Continue Reading

References

Mar 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·R LupuM E Lippman
May 22, 1992·Science·W E HolmesG D Lewis
Dec 2, 1993·Nature·G D PlowmanS Buckley
Jan 1, 1996·Breast Cancer Research and Treatment·R LupuC Tang
Nov 5, 1997·Nature Genetics·D BroccoliT de Lange
Feb 26, 1998·Cell·B van SteenselT de Lange
May 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·T Ishibashi, S J Lippard
Nov 20, 1998·Science·S SmithT de Lange
Jan 1, 1999·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·K AncelinE Gilson
May 25, 1999·Cell·J D GriffithT de Lange
Jul 20, 1999·The Journal of Biological Chemistry·A Bianchi, T de Lange
Dec 2, 1999·Nature Genetics·S H KimJ Campisi
Feb 12, 2000·Molecular and Cellular Biology·A SmogorzewskaT de Lange
Sep 6, 2000·Nature Genetics·E González-SuárezM A Blasco
Nov 9, 2000·Current Biology : CB·S Smith, T de Lange
Dec 6, 2000·The Journal of Experimental Medicine·F A GoytisoloM A Blasco
Mar 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·K H LeeR A DePinho
Sep 27, 2001·Cell·E H Blackburn
Oct 24, 2001·Experimental Gerontology·J CampisiM Rubio
Feb 19, 2002·Oncogene·Titia de Lange
Mar 30, 2002·Science·Jan KarlsederTitia de Lange
Jul 9, 2002·The Journal of Biological Chemistry·Lynne W ElmoreShawn E Holt
Nov 1, 2002·The Journal of Biological Chemistry·Rafael RamírezMaría A Blasco
Jan 25, 2003·European Journal of Biochemistry·Sabita N SaldanhaTrygve O Tollefsbol
May 22, 2003·Cancer Letters·Jan Karlseder
Jun 7, 2003·Trends in Cell Biology·Maria A Blasco, William C Hahn
Oct 21, 2003·Molecular Biology of the Cell·Bibo Li, Titia de Lange
Feb 26, 2004·The American Journal of Pathology·Alan K MeekerPedram Argani
Mar 10, 2004·Nucleic Acids Research·Rieko Ohki, Fuyuki Ishikawa
Apr 22, 2004·The Journal of Biological Chemistry·Matthew S O'ConnorZhou Songyang
May 15, 2004·Molecular and Cellular Biology·Kyungjae MyungEric A Hendrickson
Jun 11, 2004·Annual Review of Biochemistry·Agata Smogorzewska, Titia de Lange
Jul 10, 2004·Experimental Cell Research·Miguel A RubioJudith Campisi
Aug 5, 2004·The Journal of Biological Chemistry·Sahn-ho KimJudith Campisi
Aug 10, 2004·Nature Genetics·Koei ChinStephen J Lockett
Sep 24, 2004·The Journal of Biological Chemistry·Dan LiuZhou Songyang
Oct 20, 2004·Cancer Research·Isabel JacoMaría A Blasco
Jun 25, 2005·Journal of Cell Science·Catherine LeBel, Raymund J Wellinger
Sep 2, 2005·Nature Reviews. Genetics·Maria A Blasco
Sep 17, 2005·Genes & Development·Titia de Lange

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Citations

Oct 23, 2020·International Journal of Molecular Sciences·Adriana PapadimitropoulouRuth Lupu
Feb 19, 2021·Cellular and Molecular Life Sciences : CMLS·Semih Can AkincilarVinay Tergaonkar

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Methods Mentioned

BETA
transfection
co-immunoprecipitation
chromosomal aberrations
PCR
electrophoresis
Protein Assay

Software Mentioned

ImageQuant
Image
NIH Image
- QuaNT

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