The impact of the MYB-NFIB fusion proto-oncogene in vivo

Oncotarget. 2016 May 31;7(22):31681-8. doi: 10.18632/oncotarget.9426.

Abstract

Recurrent fusion of the v-myb avian myelobastosis viral oncogene homolog (MYB) and nuclear factor I/B (NFIB) generates the MYB-NFIB transcription factor, which has been detected in a high percentage of individuals with adenoid cystic carcinoma (ACC). To understand the functional role of this fusion protein in carcinogenesis, we generated a conditional mutant transgenic mouse that expresses MYB-NFIB along with p53 mutation in tissues that give rise to ACC: mammary tissue, salivary glands, or systemically in the whole body. Expression of the oncogene in mammary tissue resulted in hyperplastic glands that developed into adenocarcinoma in 27.3% of animals. Systemic expression of the MYB-NFIB fusion caused more rapid development of this breast phenotype, but mice died due to abnormal proliferation in the glomerular compartment of the kidney, which led to development of glomerulonephritis. These findings suggest the MYB-NFIB fusion is oncogenic and treatments targeting this transcription factor may lead to therapeutic responses in ACC patients.

Keywords: GEMM; MYB-NFIB; adenoid cystic carcinoma; breast; salivary.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Animals
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Fusion*
  • Genes, p53
  • Genetic Predisposition to Disease
  • Glomerulonephritis / genetics
  • Glomerulonephritis / metabolism
  • Glomerulonephritis / pathology
  • Hyperplasia
  • Mammary Neoplasms, Experimental / genetics*
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Oncogene Proteins, Fusion / genetics*
  • Oncogene Proteins, Fusion / metabolism
  • Phenotype
  • Salivary Glands / metabolism
  • Salivary Glands / pathology
  • Time Factors

Substances

  • MYB-NFIB fusion protein, human
  • Oncogene Proteins, Fusion