Developmental context determines latency of MYC-induced tumorigenesis

Shelly Beer, Anders Zetterberg, Rebecca A. Ihrie, Ryan A. McTaggart, Qiwei Yang, Nicole Bradon, Constadina Arvanitis, Laura D. Attardi, Sandy Feng, Boris Ruebner, Robert Cardiff, Dean W. Felsher

Research output: Contribution to journalArticle

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Abstract

One of the enigmas in tumor biology is that different types of cancers are prevalent in different age groups. One possible explanation is that the ability of a specific oncogene to cause tumorigenesis in a particular cell type depends on epigenetic parameters such as the developmental context. To address this hypothesis, we have used the tetracycline regulatory system to generate transgenic mice in which the expression of a c-MYC human transgene can be conditionally regulated in murine hepatocytes. MYC's ability to induce tumorigenesis was dependent upon developmental context. In embryonic and neonatal mice, MYC overexpression in the liver induced marked cell proliferation and immediate onset of neoplasia. In contrast, in adult mice MYC overexpression induced cell growth and DNA replication without mitotic cell division, and mice succumbed to neoplasia only after a prolonged latency. In adult hepatocytes, MYC activation failed to induce cell division, which was at least in part mediated through the activation of p53. Surprisingly, apoptosis is not a barrier to MYC inducing tumorigenesis. The ability of oncogenes to induce tumorigenesis may be generally restrained by developmentally specific mechanisms. Adult somatic cells have evolved mechanisms to prevent individual oncogenes from initiating cellular growth, DNA replication, and mitotic cellular division alone, thereby preventing any single genetic event from inducing tumorigenesis. Copyright:

Original languageEnglish (US)
JournalPLoS Biology
Volume2
Issue number11
DOIs
StatePublished - Nov 1 2004

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carcinogenesis
Carcinogenesis
Chemical activation
Cells
oncogenes
Oncogenes
DNA
Cell proliferation
Cell growth
Tetracycline
neoplasms
Liver
mice
Tumors
DNA replication
DNA Replication
Cell Division
hepatocytes
cell division
Apoptosis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Beer, S., Zetterberg, A., Ihrie, R. A., McTaggart, R. A., Yang, Q., Bradon, N., ... Felsher, D. W. (2004). Developmental context determines latency of MYC-induced tumorigenesis. PLoS Biology, 2(11). https://doi.org/10.1371/journal.pbio.0020332

Developmental context determines latency of MYC-induced tumorigenesis. / Beer, Shelly; Zetterberg, Anders; Ihrie, Rebecca A.; McTaggart, Ryan A.; Yang, Qiwei; Bradon, Nicole; Arvanitis, Constadina; Attardi, Laura D.; Feng, Sandy; Ruebner, Boris; Cardiff, Robert; Felsher, Dean W.

In: PLoS Biology, Vol. 2, No. 11, 01.11.2004.

Research output: Contribution to journalArticle

Beer, S, Zetterberg, A, Ihrie, RA, McTaggart, RA, Yang, Q, Bradon, N, Arvanitis, C, Attardi, LD, Feng, S, Ruebner, B, Cardiff, R & Felsher, DW 2004, 'Developmental context determines latency of MYC-induced tumorigenesis', PLoS Biology, vol. 2, no. 11. https://doi.org/10.1371/journal.pbio.0020332
Beer S, Zetterberg A, Ihrie RA, McTaggart RA, Yang Q, Bradon N et al. Developmental context determines latency of MYC-induced tumorigenesis. PLoS Biology. 2004 Nov 1;2(11). https://doi.org/10.1371/journal.pbio.0020332
Beer, Shelly ; Zetterberg, Anders ; Ihrie, Rebecca A. ; McTaggart, Ryan A. ; Yang, Qiwei ; Bradon, Nicole ; Arvanitis, Constadina ; Attardi, Laura D. ; Feng, Sandy ; Ruebner, Boris ; Cardiff, Robert ; Felsher, Dean W. / Developmental context determines latency of MYC-induced tumorigenesis. In: PLoS Biology. 2004 ; Vol. 2, No. 11.
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