Transgenic overexpression of the oncofetal RNA binding protein KOC leads to remodeling of the exocrine pancreas

Gastroenterology. 2003 Jun;124(7):1901-14. doi: 10.1016/s0016-5085(03)00402-5.


Background & aims: To elucidate the function of the oncofetal RNA-binding protein, K-homologous (KH) domain containing protein overexpressed in cancer (KOC), we studied the effect of a constitutive reexpression of KOC in transgenic mice.

Methods: Transgenic mouse lines expressing KOC under the control of the mouse metallothionein promoter were generated and were shown to express the 69-kilodalton protein. Two mouse lines with moderate to strong gene expression of the transgene were further analyzed.

Results: The pancreas of KOC-transgenic mice showed progressive morphologic alterations, including an increased proliferation of acinar cells, acinar-ductal metaplasia, net loss of acinar tissue, and the appearance of numerous interstitial cells. Acinar-ductal metaplasia led to the development of duct-like structures exhibiting the characteristics of normal intralobular ducts. Interstitial cells expressed markers of endocrine or ductal differentiation. Nerve growth factor alpha (NGF-alpha) and the GTPase kir/Gem were identified as potential targets of KOC by expression profiling analyses.

Conclusions: Reexpression of KOC in the transgenic model is apparently incompatible with the maintenance of a fully differentiated, adult acinar phenotype and may lead to a more fetal ductal phenotype via acinar-ductal metaplasia. This and the appearance of interstitial cells with a ductal and endocrine differentiation capacity suggest that transgenic reexpression of the oncofetal gene KOC may recapitulate a developmental program active during embryogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Collagen Type I / analysis
  • Fibronectins / analysis
  • Immunohistochemistry
  • Matrix Metalloproteinase 7 / analysis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Oligonucleotide Array Sequence Analysis
  • Pancreas / embryology*
  • Pancreas / pathology*
  • RNA-Binding Proteins / analysis
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / physiology*
  • Transforming Growth Factor alpha / analysis


  • Collagen Type I
  • Fibronectins
  • Igf2bp3 protein, mouse
  • RNA-Binding Proteins
  • Transforming Growth Factor alpha
  • Matrix Metalloproteinase 7