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

Thordur Oskarsson , Marieke Alida Gertruda Essers , Nicole Dubois , Sandra Offner , Christelle Dubey , Catherine Roger , Daniel Metzger (1) , Pierre Chambon (1) , Edith Hummler , Peter Beard , Andreas Trumpp

1 IGBMC - Institut de génétique et biologie moléculaire et cellulaire

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.

Domaines: Biologie moléculaire

Thordur Oskarsson, Marieke Alida Gertruda Essers, Nicole Dubois, Sandra Offner, Christelle Dubey, et al.. Skin epidermis lacking the c-Myc gene is resistant to Ras-driven tumorigenesis but can reacquire sensitivity upon additional loss of the p21Cip1 gene.. Genes and Development, 2006, 20 (15), pp.2024-9. ⟨10.1101/gad.381206⟩. ⟨hal-00188093⟩