Skip to main content
Log in

Immunohistochemically demonstrated variation in expression of cathepsin E between uracil-induced papillomatosis and N-butyl-N-(4-hydroxybutyl)nitrosamine-induced preneoplastic and neoplastic changes in rat urinary bladder

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Expression of rat urinary bladder cathepsin E in benign papillomatosis induced by uracil and various stages of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced carcinogenesis was investigated immunohistochemically. Seven-week-old, male F344/DuCrj rats were used. In the normal urothelium of control rats, cathepsin E stained in all layers of cells, although in umbrella cells and some basal cells the reaction was relatively weak. In rats given a diet containing 3% uracil for 5 weeks immunoreactivity of cathepsin E in uracil-induced papillomatosis was consistently homogeneous in all layers, but weaker than in normal urothelium. In rats given 0.05% BBN in drinking water for 12 weeks and subsequently maintained without treatment for 48 weeks cells with little cathepsin E, never observed in normal urothelium, appeared at 5 weeks above the basement membrane in the earliest stage of BBN-induced urinary bladder cancer (simple hyperplasia). Throughout the neoplastic process, groups of cells with a little cathepsin E were randomly distributed, with expression in the urothelium being markedly unstable. Almost all areas of squamous cell proliferation in TCC were negative for cathepsin E. Instability of cathepsin E expression in rat urothelium therefore appears characteristic for carcinogenesis and offers the possibility of using this feature as an early biomarker for urinary bladder carcinogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Fukushima S, Murasaki G, Hirose M, Nakanishi K, Hasegawa R, Ito N (1982) Histopathological analysis of preneoplastic changes during N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis in rats. Acta Pathol Jpn 32:243–250

    Google Scholar 

  2. Ito N, Tsuda H, Tatematsu M, Inoue T, Tagawa Y, Aoki T, Uwagawa S, Kagawa M, Ogiso T, Masui T, Imaida K, Fukushima S, Asamoto M (1988) Enhancing effect of various hepatocarcinogens on induction of preneoplastic glutathione S- transferase placental form positive foci in rats-an approach for a new medium-term bioassay system. Carcinogenesis 9:387–394

    Google Scholar 

  3. Jupp RA, Richards AD, Kay J, Dunn BM, Wyckoff JB, Samloff IM, Yamamoto K (1988) Identification of the aspartic proteinases from human erythrocyte membranes and gastric mucosa (slow-moving proteinase) as catalytically equivalent to cathepsin E. Biochem J 254:895–898

    Google Scholar 

  4. Kunze E (1979) Development of urinary bladder cancer in the rat. Curr Top Pathol 67:145–232

    Google Scholar 

  5. Muto N, Yamamoto M, Tani S (1987) Comparative studies of two types of acid proteases from rat gastric mucosa and spleen. J Biochem 101:1069–1075

    Google Scholar 

  6. Muto N, Yamamoto M, Tani S, Yonezawa S (1988) Characteristic distribution of cathepsin E which immunologically cross-reacts with the 86-kDa acid proteinase from rat gastric mucosa. J Biochem 103:629–632

    Google Scholar 

  7. Sakai H, Saku T, Kato Y, Yamamoto K (1989) Quantitation and immunohistochemical localization of cathepsins E and D in rat tissues and blood cells. Biochim Biophys Acta 991:367–375

    Google Scholar 

  8. Saku T, Sakai H, Shibata Y, Kato Y, Yamamoto K (1991) An immunocytochemical study on distinct intracellular localization of cathepsin E and cathepsin D in human gastric cells and various rat cells. J Biochem 110:956–964

    Google Scholar 

  9. Shirai T, Ikawa E, Fukushima S, Masui T, Ito N (1986) Uracil-induced urolithiasis and the development of reversible papillomatosis in the urinary bladder of F344 rats. Cancer Res 46:2062–2067

    Google Scholar 

  10. Shirai T, Fukushima S, Tagawa Y, Okumura M, Ito N (1989) Cell proliferation induced by uracil-calculi and subsequent development of reversible papillomatosis in the rat urinary bladder. Cancer Res 49:378–383

    Google Scholar 

  11. Tatematsu M, Fukushima S, Aoki T, Mera Y, Inoue T, Ito N (1987) Patterns of epithelial proliferation revealed by continuous administration of bromodeoxyuridine during urinary bladder carcinogenesis in rats. Jpn J Cancer Res 78:879–882

    Google Scholar 

  12. Tatematsu M, Furihata C, Katsuyama T, Mera Y, Inoue T, Matsushima T, Ito N (1987) Immunohistochemical demonstration of pyloric gland-type cells with low-pepsinogen isozyme 1 in preneoplastic and neoplastic tissues of rat stomachs treated with N-methyl-N'-nitro-N-nitrosoguanidine. J Natl Cancer Inst 78:771–777

    Google Scholar 

  13. Tatematsu M, Iwata H, Ichinose M, Kakei N, Tsukada S, Miki K, Imai S, Imaida K (1993) Markers of surface mucous cell type human gastric cancer cells: Galactose oxidase-Schiff reactive mucins, monoclonal antibody SH-9 reactive mucins and cathepsin E. Acta Pathol Jpn 43:500–506

    Google Scholar 

  14. Vanderlaan M, Fong S, King EB (1982) Histochemistry of NADH diaphorase and r-glutamyltranspeptidase in rat bladder tumors. Carcinogenesis 3:397–402

    Google Scholar 

  15. Yonezawa S, Tanaka T, Muto N, Tani S (1987) Immunochemical similarity between a gastric mucosa non-pepsin acid proteinase and neutrophil cathepsin E of the rat. Biochem Biophys Res Commun 144:1251–1256

    Google Scholar 

  16. Yonezawa S, Fujii K, Maejima Y, Tamoto K, Mori Y, Muto N (1988) Further studies on rat cathepsin E: subcellular localization and existence of the active subunit form. Arch Biochem Biophys 267:176–183

    Google Scholar 

  17. Yonezawa S, Takahashi T, Ichinose M, Miki K, Tanaka J, Gasa S (1990) Structural studies of rat cathepsin E: amino-terminal structure and carbohydrate units of mature enzyme. Biochem Biophys Res Commun 166:1032–1038

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yamamoto, S., Masui, T., Inoue, H. et al. Immunohistochemically demonstrated variation in expression of cathepsin E between uracil-induced papillomatosis and N-butyl-N-(4-hydroxybutyl)nitrosamine-induced preneoplastic and neoplastic changes in rat urinary bladder. Vichows Archiv A Pathol Anat 427, 589–594 (1996). https://doi.org/10.1007/BF00202890

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00202890

Key words

Navigation