Genetic Analysis of Myc and Telomerase Interactions In Vivo

  • Flores I
  • Evan G
  • Blasco M
  • 36

    Readers

    Mendeley users who have this article in their library.
  • 30

    Citations

    Citations of this article.

Abstract

Myc is a transcription factor with pleiotropic effects on tumorigenesis which are likely to be mediated by its target genes. A known Myc transcriptional target is the catalytic subunit of telomerase, Tert. However, the contribution of Tert activation to Myc-induced tumorigenesis in vivo remains unknown. In this study, we addressed the role of telomerase in Myc-induced skin papillomatosis by using compound mice with a switchable Myc gene, Inv-MycERTAM mice, in combination with either telomerase deficiency (Terc-/-) or telomerase overexpression (K5-mTert) in the skin. We first demonstrated that Myc activates telomerase in the skin. With Inv-MycERTAM x Terc-/- mice, we further showed that this telomerase activation is partially required to elicit a full hyperplastic Myc-induced response. The presence of critically short telomeres in late-generation Inv-MycERTAM x Terc-/- mice further reduced the skin lesion induced by Myc. On the other hand, telomerase overexpression in the skin of K5-mTert mice augments Myc-induced hyperplasia in the absence of changes in telomere length, suggesting a direct role of telomerase in the Myc protumorigenic response. Taken together, these results highlight telomerase as a mediator of Myc-induced papillomatosis and suggest telomerase as a putative therapeutic target for Myc-dependent lesions.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • I. Flores

  • G. Evan

  • M. A. Blasco

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free