Skin epidermis lacking the c-Myc gene is resistant to Ras-driven tumorigenesis but can reacquire sensitivity upon additional loss of the p21Cip1 gene.

Abstract:

:The target gene(s) required for Myc-mediated tumorigenesis are still elusive. Here we show that while endogenous c-Myc is surprisingly dispensable for skin homeostasis and TPA-induced hyperplasia, c-Myc-deficient epidermis is resistant to Ras-mediated DMBA/TPAinduced tumorigenesis. This is mechanistically linked to p21(Cip1), which is induced in tumors by the activated Ras-ERK pathway but repressed by c-Myc. Acute elimination of c-Myc in established tumors leads to the up-regulation of p21(Cip1), and epidermis lacking both p21(Cip1) and c-Myc reacquires normal sensitivity to DMBA/TPA-induced tumorigenesis. This identifies c-Myc-mediated repression of p21(Cip1) as a key step for Ras-driven epidermal tumorigenesis.

journal_name

Genes Dev

journal_title

Genes & development

authors

Oskarsson T,Essers MA,Dubois N,Offner S,Dubey C,Roger C,Metzger D,Chambon P,Hummler E,Beard P,Trumpp A

doi

10.1101/gad.381206

subject

Has Abstract

pub_date

2006-08-01 00:00:00

pages

2024-9

issue

15

eissn

0890-9369

issn

1549-5477

pii

20/15/2024

journal_volume

20

pub_type

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