Open Access Research article

Deciphering c-MYC-regulated genes in two distinct tissues

Samuel C Robson1, Lesley Ward2, Helen Brown2, Heather Turner3, Ewan Hunter4, Stella Pelengaris5 and Michael Khan6*

Author Affiliations

1 Wellcome Trust/Cancer Research UK Gurdon Institute, Cambridge, CB2 1QN, UK

2 Molecular Biology Service, University of Warwick, CV4 7AL, UK

3 Pfizer Global R & D, Kent, CT13 9NJ, UK

4 Genstruct Inc, One Alewife Center, Cambridge, MA, 02140, USA

5 Warwick Medical School, University of Warwick, CV4 7AL, UK

6 Biomedical Research Institute, Department of Biological Sciences, University of Warwick, CV4 7AL, UK

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BMC Genomics 2011, 12:476  doi:10.1186/1471-2164-12-476

Published: 30 September 2011



The transcription factor MYC is a critical regulator of diverse cellular processes, including both replication and apoptosis. Differences in MYC-regulated gene expression responsible for such opposing outcomes in vivo remain obscure. To address this we have examined time-dependent changes in global gene expression in two transgenic mouse models in which MYC activation, in either skin suprabasal keratinocytes or pancreatic islet β-cells, promotes tissue expansion or involution, respectively.


Consistent with observed phenotypes, expression of cell cycle genes is increased in both models (albeit enriched in β-cells), as are those involved in cell growth and metabolism, while expression of genes involved in cell differentiation is down-regulated. However, in β-cells, which unlike suprabasal keratinocytes undergo prominent apoptosis from 24 hours, there is up-regulation of genes associated with DNA-damage response and intrinsic apoptotic pathways, including Atr, Arf, Bax and Cycs. In striking contrast, this is not the case for suprabasal keratinocytes, where pro-apoptotic genes such as Noxa are down-regulated and key anti-apoptotic pathways (such as Igf1-Akt) and those promoting angiogenesis are up-regulated. Moreover, dramatic up-regulation of steroid hormone-regulated Kallikrein serine protease family members in suprabasal keratinocytes alone could further enhance local Igf1 actions, such as through proteolysis of Igf1 binding proteins.


Activation of MYC causes cell growth, loss of differentiation and cell cycle entry in both β-cells and suprabasal keratinocytes in vivo. Apoptosis, which is confined to β-cells, may involve a combination of a DNA-damage response and downstream activation of pro-apoptotic signalling pathways, including Cdc2a and p19Arf/p53, and downstream targets. Conversely, avoidance of apoptosis in suprabasal keratinocytes may result primarily from the activation of key anti-apoptotic signalling pathways, particularly Igf1-Akt, and induction of an angiogenic response, though intrinsic resistance to induction of p19Arf by MYC in suprabasal keratinocytes may contribute.