Heterogeneity in MYC-induced mammary tumors contributes to escape from oncogene dependence

J. Y. Leung, E. R. Andrechek, Robert Cardiff, J. R. Nevins

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

A hallmark of human cancer is heterogeneity, reflecting the complex series of changes resulting in the activation of oncogenes coupled with inactivation of tumor suppressor genes. Breast cancer is no exception and indeed, many studies have revealed considerable complexity and heterogeneity in the population of primary breast tumors and substantial changes in a recurrent breast tumor that has acquired metastatic properties and drug resistance. We have made use of a Myc-inducible transgenic mouse model of breast cancer in which elimination of Myc activity following tumor development initially leads to a regression of a subset of tumors generally followed by de novo Myc-independent growth. We have observed that tumors that grow independent of Myc expression have gene profiles that are distinct from the primary tumors with characteristics indicative of an epithelial-mesenchymal transition (EMT) phenotype. Phenotypic analyses of Myc-independent tumors confirm the acquisition of an EMT phenotype suggested to be associated with invasive and migratory properties in human cancer cells. Further genomic analyses reveal mouse mammary tumors growing independent of myc have a higher probability of exhibiting a gene signature similar to that observed for human tumor-initiating cells. Collectively, the data reveal genetic alterations that underlie tumor progression and an escape from Myc-dependent growth in a transgenic mouse model that can provide insights to what occurs in human cancers as they acquire drug resistance and metastatic properties.

Original languageEnglish (US)
Pages (from-to)2545-2554
Number of pages10
JournalOncogene
Volume31
Issue number20
DOIs
StatePublished - May 17 2012

Fingerprint

Oncogenes
Breast Neoplasms
Neoplasms
Epithelial-Mesenchymal Transition
Drug Resistance
Transgenic Mice
Tumor Escape
Phenotype
Neoplastic Stem Cells
Population Characteristics
Growth
Tumor Suppressor Genes
Transcriptome
Genes

Keywords

  • cancer
  • EMT
  • mammary
  • mouse
  • MYC

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Heterogeneity in MYC-induced mammary tumors contributes to escape from oncogene dependence. / Leung, J. Y.; Andrechek, E. R.; Cardiff, Robert; Nevins, J. R.

In: Oncogene, Vol. 31, No. 20, 17.05.2012, p. 2545-2554.

Research output: Contribution to journalArticle

Leung, J. Y. ; Andrechek, E. R. ; Cardiff, Robert ; Nevins, J. R. / Heterogeneity in MYC-induced mammary tumors contributes to escape from oncogene dependence. In: Oncogene. 2012 ; Vol. 31, No. 20. pp. 2545-2554.
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