Enforced expression of FGF-7 promotes epithelial hyperplasia whereas a dominant negative FGFR2iiib promotes the emergence of neuroendocrine phenotype in prostate glands of transgenic mice

Differentiation. 2002 Dec;70(9-10):624-32. doi: 10.1046/j.1432-0436.2002.700915.x.


The minimal rat probasin (PB) promoter was used to target expression of human fibroblast growth factor-7 (FGF-7)/keratinocyte growth factor (KGF) directly to prostatic epithelium of transgenic mice, converting FGF-7 from a paracrine to an autocrine factor. Four independent lines were established that expressed the transgene (PKS) in the prostate. Upon histologic analysis, the prostatic epithelium of PKS mice was found to be hyperplastic. Many of the prostatic ducts were filled with secretory epithelial cells tightly associated with a highly enfolded basement membrane. Distortions of the ductal smooth muscle layer were also observed. Prostates from year-old PKS mice had significantly more abnormal ducts than their wild-type nontransgenic littermates. The minimal rat PB promoter was also used to target a truncated FGFR2iiib receptor to prostatic epithelium to functionally abrogate endogenous FGF-7 signaling. Three lines were established that expressed the transgene (KDNR) in the prostate. Upon dissection it was noted that all four lobes of the prostates of KDNR mice were present but smaller in size. Histologic analysis indicated that the epithelium in many of the prostatic ducts was disorganized and contained numerous rounded cytokeratin-positive cells that were not tightly associated with the basement membrane. The stroma was disorganized and did not form a tight layer of smooth muscle around the epithelial ducts. Surprisingly, abrogation of FGF signaling in KDNR mice correlated with the emergence of a neuroendocrine-like phenotype that was not observed as a consequence of enforced FGF-7 expression in the PKS mice.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Androgen-Binding Protein / genetics
  • Animals
  • Autocrine Communication / genetics
  • Cell Differentiation* / genetics
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors / genetics*
  • Fibroblast Growth Factors / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Paracrine Communication / genetics
  • Promoter Regions, Genetic
  • Prostate / pathology*
  • Prostate / physiology
  • Prostatic Hyperplasia / etiology
  • Prostatic Hyperplasia / genetics*
  • Prostatic Hyperplasia / pathology
  • Rats
  • Receptor, Fibroblast Growth Factor, Type 2
  • Receptors, Fibroblast Growth Factor / genetics*
  • Receptors, Fibroblast Growth Factor / metabolism


  • Androgen-Binding Protein
  • FGF7 protein, human
  • Fgf7 protein, mouse
  • Fgf7 protein, rat
  • Receptors, Fibroblast Growth Factor
  • probasin
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors
  • Receptor, Fibroblast Growth Factor, Type 2
  • keratinocyte growth factor receptor