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Immunological characterization and activity of transglutaminases in human normal and malignant prostate and in prostate cancer cell lines

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Abstract

Using biochemical assays, we compared enzyme activities with the immunoreactivity of antibodies against rat seminal transglutaminase (TGase), human erythrocyte TGase and guinea pig liver TGase in human normal prostate, primary prostatic carcinomas and prostatic carcinoma cell lines. Glandular cells of the epithelium were only exceptionally positive with the antibody against (rat) secretory TGase. Using the antibodies against tissue-type TGase, most immunoreactive cells were found in the basal cell layer of prostatic epithelium as well as in stroma (fibroblasts, endothelial cells), whereas immunoreactive glandular cells were sparse. In the case of benign prostatic hyperplasia, few, irregularly distributed secretory cells along with a small number of stromal cells were also immunoreactive with the tissue-type TGase antibody. In dedifferentiated carcinomas, immunoreactive cells were nearly completely absent. Of the prostate cancer cell lines, the LNCaP line showed neither TGase enzyme activity nor immunoreactivity, whereas the PC-3 cell line displayed significant enzyme activity and immunoreactivity. No hormone-dependent changes in either enzyme activity or immunoreactivity were recorded after in vitro treatment of the respective cell lines with estrogens, androgens and antiandrogens. As there is no correlation between androgen deprivation and TGase expression in nonmalignant and malignant human prostatic epithelial cells, TGase activity more likely indicates cellular lesions and consecutive repair mechanisms.

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References

  1. Achyuthan KE, Greenberg CS (1987) Identification of a GTP-binding site on guinea pig liver transglutaminase. Role of GTP and calcium ions in modulating activity. J Biol Chem 262:1901

    Google Scholar 

  2. Aeschlimann D, Paulsson M (1991) Cross-linking of lamininnidogen complexes by tissue transglutaminase. A novel mechanism for basement membrane stabilization. J Biol Chem 266:15308

    Google Scholar 

  3. Aumüller G, Seitz J, Bischof W (1983) Immunohistochemical study on the initiation of acid phosphatase secretion in the human prostate. J Androl 4:183

    Google Scholar 

  4. Bacher M, Rausch U, Goebel HW, Polzar B, Mannherz HG, Aumüller G (1993) Hormonal regulation of stromal cells from rat ventral prostate during androgen deprivation and estrogen treatment. Exp Clin Endocrinol 101:79

    Google Scholar 

  5. Barnes RN, Bungay PJ, Elliot BM, Walton PL, Griffin M (1985) Alterations in the distribution and activity of transglutaminase during tumor growth and metastasis. Carcinogenesis 6:456

    Google Scholar 

  6. Barsigian C, Stern AM, Martinez J (1991) Tissue (type II) transglutaminase covalently incorporates itself, fibrinogen, or fibronectin into high molecular weight complexes on the extracellular surface of isolated hepatocytes. J Biol Chem 266:22501

    Google Scholar 

  7. Bergamini CM, Signorini M, Poltronieri L (1987) Inhibition of erythrocyte transglutaminase by GTP. Biochim Biophys Acta 916:149

    Google Scholar 

  8. Birckbichler PJ, Orr GR, Conway E, Patterson MK Jr (1977) Transglutaminase activity in normal and transformed cells. Cancer Res 37:1340

    Google Scholar 

  9. Birckbichler PJ, Orr GR, Patterson MK Jr, Conway E, Carter HA (1981) Increase in proliferative markers after inhibition of transglutaminase. Proc Natl Acad Sci USA 78:5005

    Google Scholar 

  10. Bradford M (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248

    Google Scholar 

  11. Brenner SC, Wold F (1978) Human erythrocyte transglutaminase. Purification and properties. Biochim Biophys Acta 522:74

    Google Scholar 

  12. Bungay PJ, Potter JM, Griffin M (1984) A role for polyamines in stimulus/secretion coupling in the pancreatic β-cell. Biosci Rep 4:869

    Google Scholar 

  13. Byrd JC, Lichti U (1987) Two types of transglutaminase in the PC 12 pheochromocytoma cell line. J Biol Chem 262:11699

    Google Scholar 

  14. Candido EPM, Reeves R, Davie JR (1978) Sodium butyrate inhibits histone deacetylation in cultured cells. Cell 14:105

    Google Scholar 

  15. Eicheler W, Tuohimaa P, Vilja P, Adermann K, Forssmann WG, Aumüller G (1994) Immunocytochemical localization of human 5α-reductase 2 with polyclonal antibodies in androgen target and non-target human tissues. J Histochem Cytochem 42:667

    Google Scholar 

  16. El Alaoui S, Legastelois S, Roch AM, Qash G (1991) Transglutaminase activity and N ε (γ-glutamyl) lysine isopeptide levels during cell growth: an enzymic and immunologic study. Int J Cancer 48:221

    Google Scholar 

  17. Fair WR (1992) The natural history of locally confined prostate cancer: a review. Prostate [Suppl] 4:79

    Google Scholar 

  18. Fésüs L, Davies PJA, Piacentini M (1991) Apoptosis: molecular mechanisms in programmed cell death. Eur J Cell Biol 56:170

    Google Scholar 

  19. Folk JE, Chung SI (1985) Molecular and catalytic properties of transglutaminases. Adv Enzymol 38:109

    Google Scholar 

  20. Graham RC, Karnovsky MJ (1966) The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney. J Histochem Cytochem 14:291

    Google Scholar 

  21. Greenberg CS, Birckbichler PJ, Rice RH (1991) Transglutaminases: multifunctional cross-linking enzymes that stabilize tissues. FASEB J 5:3071

    Google Scholar 

  22. Grundmann U, Amann E, Zettelmeissl G, Kupper HA (1986) Characterization of cDNA coding for human factor XIIIa. Proc Natl Acad Sci USA 83:8024

    Google Scholar 

  23. Hand D, Elliot BM, Griffin M (1987) Expression of the cytosolic and particulate forms of transglutaminase during chemically induced rat liver carcinogenesis. Biochim Biophys Acta 1053:13

    Google Scholar 

  24. Ho KC, Quarmby VE, French FS, Wilson EM (1992) Molecular cloning of rat prostate transglutaminase complementary DNA. J Biol Chem 267:12660

    Google Scholar 

  25. Ichinose A, Bottenus RE, Davie EW (1990) Structure of transglutaminases. J Biol Chem 265:13411

    Google Scholar 

  26. Ikura K, Nasu T, Yokota H, Tsuchiya Y, Sasaki R, Chiba H (1988) Amino acid sequence of guinea pig liver transglutaminase from its cDNA sequences. Biochemistry 27:2898

    Google Scholar 

  27. Piacentini M, Fésüs L, Farace MG, Ghibelli L, Piredda L, Mellino G (1991) The expression of “tissue” transglutaminase in two human cancer cell lines is related with the programmed cell death (apoptosis). Eur J Cell Biol 54:246

    Google Scholar 

  28. Polakowska R, Herting E, Goldsmith LA (1991) Isolation of cDNA for human epidermal type I transglutaminase. J Invest Dermatol 96:285

    Google Scholar 

  29. Romijn JC, Verkoelen CF, Schroeder FH (1989) Analysis of transglutaminase activities in prostate cancer cells: relationship with metastatic potential. Urol Res 17:331

    Google Scholar 

  30. Seitz J, Keppler C, Hüntemann S, Rausch U, Aumüller G (1991) Purification and molecular characterization of a secretory transglutaminase from coagulating gland of the rat. Biochim Biophys Acta 1078:139

    Google Scholar 

  31. Slife CW, Dorsett MD, Tillotson ML (1985) Subcellular location and identification of a large molecular weight substrate for the liver plasma membrane transglutaminase. J Biol Chem 261:3451

    Google Scholar 

  32. Steinhoff M, Seitz J, Eicheler W, Hoffbauer G, Aumüller G (1992) Hormone-dependence of apocrine secretion in rat coagulating gland. Eur J Cell Biol 57 [Suppl]:36

    Google Scholar 

  33. Sternberger LA, Hardy PH Jr, Cuculis JJ, Meyer HG (1970) The unlabeled antibody enzyme method of immunohistochemistry. J Histochem Cytochem 18:315

    Google Scholar 

  34. Thomázy V, Fésüs L (1989) Differential expression of tissue transglutaminase in human cells. An immunohistochemical study. Cell Tissue Res 255:215

    Google Scholar 

  35. Towbin H, Staehelin T, Gordon J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 76:4350

    Google Scholar 

  36. Turnock K, Bulmer JN, Gray C (1990) Phenotypic characterization of macrophage subpopulations and localization of factor XIII in the stromal cells of carcinomas. Histochem J 22:661

    Google Scholar 

  37. Upchurch HF, Conway E, Patterson MK Jr, Maxwell MD (1991) Localization of cellular transglutaminase on the extracellular matrix after wounding: characteristics of the matrix bound enzyme. J Cell Physiol 149:375

    Google Scholar 

  38. Williams-Ashman HG (1984) Transglutaminases and the clotting of mammalian seminal fluids. Mol Cell Biochem 58:51

    Google Scholar 

  39. Wunsch A, Rausch U, Seitz J, Goebel HW, Friedrichs B, Aumüller G (1992) Tissue-type transglutaminase expression in the Dunning tumor. Urol Res 21:9

    Google Scholar 

  40. Zirvi KA, Keogh JP, Slomiany A, Slomiany BL (1991) Transglutaminase activity in human colorectal carcinomas of differing metastatic potential. Cancer Lett 60:85

    Google Scholar 

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Friedrichs, B., Riedmiller, H., Goebel, HW. et al. Immunological characterization and activity of transglutaminases in human normal and malignant prostate and in prostate cancer cell lines. Urol. Res. 23, 301–310 (1995). https://doi.org/10.1007/BF00300018

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  • DOI: https://doi.org/10.1007/BF00300018

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