C-jun activation in acquired cystic kidney disease and renal cell carcinoma

J Urol. 2005 Aug;174(2):726. doi: 10.1097/01.ju.0000164656.99251.77.

Abstract

Purpose: Activator protein-1 has a central role in transducing cytokine signals. Activator protein-1 is composed of 2 proto-oncogene families, namely Jun and Fos. Of them c-Jun has been suggested to have a role in cell cycle progression and neoplastic transformation. We examined the impact of c-Jun protein activation on pathological parameters in renal cell carcinoma (RCC).

Materials and methods: The expression of total c-Jun protein and phosphorylated c-Jun protein was determined by immunohistochemistry in 72 patients with RCC, including 10 with tumor arising from acquired cystic kidney disease (ACKD) of end stage kidneys.

Results: c-Jun expression was observed in the distal but not the proximal tubules. Atypical hyperplastic cells in ACKD were positive for phosphorylated c-Jun. RCC arising in end stage kidneys was pT1 and 5 of these cases showed increased c-Jun activation. Of 62 cases arising from normally functioning kidneys 21 showed an increased degree of c-Jun activation. In localized small cell cases (pT1a) 55.5% (10 of 18) showed enhanced activation, whereas such enhanced activation was only observed in 25% (11 of 44) of more advanced cases (pT1b or greater). Therefore, c-Jun activation was considered to be related to the early carcinogenesis of RCC.

Conclusions: This study emphasizes the role that c-Jun activation has in early RCC carcinogenesis. Thus, chronic stimulation of cytokines inducing c-Jun activation may have a role in the aberrant proliferation of hyperplastic atypical cells in ACKD and RCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology
  • Female
  • Genes, jun / physiology*
  • Humans
  • Immunohistochemistry
  • Kidney Diseases, Cystic / metabolism*
  • Kidney Diseases, Cystic / pathology
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Kidney Tubules, Distal / metabolism
  • Kidney Tubules, Proximal / metabolism
  • Male
  • Middle Aged
  • Phosphorylation