Skip to main content
SpringerLink
Log in

Changes in Growth Factor Expression in the Ageing Prostate may Disrupt Epithelial–Stromal Homeostasis

  • Published:
The Histochemical Journal Aims and scope Submit manuscript

Abstract

The alterations in expression of six growth factors known to be regulators of prostatic function have been examined in the ventral lobe of prostates from young adult (14 week) and ageing (1.5 year) Wistar rats. The selected growth factors were transforming growth factor beta (TGFβ1), insulin-like growth factor I (IGF-I), insulin-like growth factor II (IGF-II), platelet derived growth factor (PDGF), basic fibroblast growth factor (FGF2) and epidermal growth factor (EGF). The extracellular matrix growth co-factor thrombospondin (TSP) was also examined. Our study demonstrated a 2.9-fold up-regulation of TGFβ1 (p<0.0001), a 2.0-fold increase in FGF2 (p<0.0002), an 8.3-fold increase in IGF-II (p<0.0007) and a 5.4-fold increase in EGF (p<0.0001) in ageing compared to adult prostate tissue. Conversely, we observed a 2.7-fold down-regulation of IGF-I (p<0.0005), a 1.7-fold decrease in PDGF (p<0.0097) and a 5.8-fold decrease in TSP (p<0.0079) in ageing rat prostate tissue. The observed alterations in growth factor expression in this study may be the result or cause of, an imbalance in the proliferative–apoptotic balance during ageing. This imbalance may explain the increase in epithelial proliferation that is characteristic of the normal ageing prostate. As in other systems it seems likely that these factors work synergistically rather than in isolation.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References cited

  • Albrecht D, Tidball J (1997) Platelet-derived growth factor-stimulated secretion of basement membrane proteins by skeletal muscle occurs by tyrosine kinase-dependent and-independent pathways. J Biol Chem 272: 2236-2244.

    Google Scholar 

  • Banerjee S, Banerjee PP, Brown TR (2000) Castration-induced apoptotic cell death in the Brown Norway rat prostate decreases as a function of age. Endocrinology 141: 821-832

    Google Scholar 

  • Barclay A (1981) The localisation of populations of lymphocytes defined by monoclonal antibodies in rat lymphoid tissues. Immunology 42: 593-600.

    Google Scholar 

  • Bishop G, Hall B, Duggin G, Horvath J, Ross-Sheil A, Tiller D (1986) Immunopathology of renal allograft rejection analysed with monoclonal antibodies to mononuclear cell markers. Kidney Int 29: 708-717.

    Google Scholar 

  • Brass A, Bernard J, Batai B, Salvi D, Rukstalis D (1995) Androgen up-regulated epidermal growth factor expression in binding affinity PC3 cell lines expressed in the human androgen receptor. Cancer Res 55: 3197-123.

    Google Scholar 

  • Cechowska-Pasko M, Palka J, Bankowski E (1996) Alterations in glycosaminoglycans in wounded skin of diabetic rats. A possible role of IGF-I, IGF-binding proteins and proteolytic activity. Acta Biochim Polon 43: 557-565.

    Google Scholar 

  • Colombel MC, Buttyan R (1995) Hormonal control of apoptosis: the rat prostate gland as a model system. Method Cell Biol 46: 369-385.

    Google Scholar 

  • Cunha GR, Alarid ET, Turner T, Donjacour AA, Boutin EL, Foster BA (1992) Normal and abnormal development of the male urogenital tract. Role of androgens, mesenchymal-epithelial interactions, and growth factors. J Androl 13: 465-475.

    Google Scholar 

  • Cunha GR, Hayward SW, Dahiya R, Foster BA (1996) Smooth muscle-epithelial interactions in normal and neoplastic prostatic development. Acta Anat 155: 63-72.

    Google Scholar 

  • Farrelly N, Lee YJ, Oliver J, Dive C, Streuli CH (1999) Extracellular matrix regulates apoptosis in mammary epithelium through a control on insulin signalling. J Cell Biol 144: 1337-1348.

    Google Scholar 

  • Gerdes MJ, Dang TD, Larsen M, Rowley DR (1998) Transforming growth factor-beta1 induces nuclear to cytoplasmic distribution of androgen receptor and inhibits androgen response in prostate smooth muscle cells. Endocrinology 139: 3569-3577.

    Google Scholar 

  • Gospodarowicz D (1990) Fibroblast growth factor and its involvement in developmental processes. Curr Topics Dev Biol 24: 57-63.

    Google Scholar 

  • Guo N, Zabrenetzky VS, Chandrasekaran L, Sipes JM, Lawler J, Krutzsch HC, Roberts DD (1998) Differential roles of protein kinase C and pertussis toxin-sensitive G-binding proteins in modulation of melanoma cell proliferation and motility by thrombospondin 1. Cancer Res 58: 3154-3162.

    Google Scholar 

  • Habib F (1994) The role of growth factors in the pathogenesis of BPH. Prog Clin Biol Res 386: 43-50.

    Google Scholar 

  • Haimovici F, Anderson DJ (1993) Effects of growth factors and growth factor-extracellular matrix interactions on mouse trophoblast outgrowth in vitro. Biol Reprod 49: 124-130.

    Google Scholar 

  • Hayward S, Rosen M, Cunha G (1997) Stromal-epithelial interactions in the normal and neoplastic prostate. Br J Urol 79(Suppl. 2): 18-26.

    Google Scholar 

  • Herrler A, Krusche C, Beier H (1998) Insulin and insulin-like growth factor-I promote rabbit blastocyst development and prevent apoptosis. Biol Reprod 59: 1302-1310.

    Google Scholar 

  • Hugo C, Pichler R, Meek R, Gordon K, Kyriakides T, Floege J, Bornstein P, Couser WG, Johnson RJ (1995) Thrombospondin 1 is expressed by proliferating mesangial cells and is up-regulated by PDGF and bFGF in vivo. Kidney Int 48: 1846-1856.

    Google Scholar 

  • Husmann I, Soulet L, Gautron J, Martelly I, Barritault D (1996) Growth factors in skeletal muscle regeneration. Cyto Growth Fact Rev 7: 249-258.

    Google Scholar 

  • Kyprianou N (1997) Role of apoptosis in development of benign prostatic hyperplasia (BPH) and prostate cancer. In: Rajesh K, ed. Prostate: Basic and Clinical Aspects. New York: CRC Press, pp. 181-199.

    Google Scholar 

  • Lea RG, Clark DA (1993) Effects of decidual cell supernatants and lymphokines on murine trophoblasts in vitro. Biol Reprod 48: 930-935.

    Google Scholar 

  • Lee C (1997) Biology of the prostatic ductal system. In: Rajesh K, ed. Prostate: Basic and Clinical Aspects. New York: Raven Press, pp. 53-71.

    Google Scholar 

  • Marengo SR, Chung LW (1994) An orthotopic model for the study of growth factors in the ventral prostate of the rat: effects of epidermal growth factor and basic fibroblast growth factor. J Androl 15: 277-286.

    Google Scholar 

  • McKeehan W (1991) Growth factor receptors and prostate cell growth. In: Issacs J, ed. Cancer Surveys. New York: Cold Spring Harbour Laboratory Press, pp. 165-173.

    Google Scholar 

  • Mori H, Maki O, Jaye M, Igarashi K, Yoshida O, Hatanaka M (1990) Increased expression of genes for basic fibroblast growth factor and transforming growth factor type beta-2 in human benign prostatic hyperplasia. Prostate 16: 71-80.

    Google Scholar 

  • Peehl D, Cohen P, Rosenfeld R (1996) The role of insulin-like growth factors in prostate biology. J Androl 17: 2-11.

    Google Scholar 

  • Pricci F, Pugliese G, Romano G, Romeo G, Locuratolo N, Pugliese F, Mene P, Galli G, Casini A, Rotella CM, Di Mario U (1996) Insulin-like growth factors I and II stimulate extracellular matrix production in human glomerular mesangial cells. Comparison with transforming growth factor-beta. Endocrinology 137: 879-885.

    Google Scholar 

  • Reiser K, Summers P, Medrano JF, Rucker R, Last J, McDonald R (1996) Effects of elevated circulating IGF-1 on the extracellular matrix in ‘high-growth’ C57BL/6J mice. Am J Physiol 271: R696-R703.

    Google Scholar 

  • Roth JJ, Gahtan V, Brown JL, Gerhard C, Swami VK, Rothman VL, Tulenko TN, Tuszynski GP (1998) Thrombospondin-1 is elevated with both intimal hyperplasia and hypercholesterolemia. J Surg Res 74: 11-16.

    Google Scholar 

  • Russell P, Bennett S, Stricker P (1998a) Growth factor involvement in progression of prostate cancer. Clin Chem 44: 705-723.

    Google Scholar 

  • Shaw T, Murphy C (1995) Leucocyte involvement in lectin-induced deciduomata formation. Cell Biol Int 19: 577-584.

    Google Scholar 

  • Sherwood E, Lee C (1995) Epidermal growth factor-related peptides and the epidermal growth factor receptor in normal and malignant prostate. World J Urol 13: 290-302.

    Google Scholar 

  • Shibata Y, Ito K, Suzuki K, Nakano K, Fukabori Y, Suzuki R, Kawabe Y, Honma, S, Yamanaka H (2000) Changes in the endocrine environment of the human prostate transition zone with ageing: simultaneous quantitative analysis of prostatic sex steroids and comparison with human prostatic histological composition. Prostate 42: 45-55.

    Google Scholar 

  • Slater M (1996) Dynamic interactions of the extracellular matrix. Histol Histopathol 11: 175-180.

    Google Scholar 

  • Slater M (1999) Mitochondrial DNA damage assessment using fluorescence microscopy quantitation. J Histotechnol 22: 17-21.

    Google Scholar 

  • Slater M, Murphy C (1999) Detection of apoptotic DNA damage in prostate hyperplasia using tyramide-amplified avidin-HRP. Histochem J 31: 747-749.

    Google Scholar 

  • Slater M, Patava J, Kingham K, Mason RS (1994) Modulation of growth factor incorporation into the extracellular matrix of human osteoblast-like cells in vitro by 17β estradiol. Am J Physiol 267: E990-E1001.

    Google Scholar 

  • Steiner M (1997) Peptide growth factors in prostate cancer. In: Rajesh K, ed. Prostate: Basic and Clinical aspects. Nw York: CRC Press, pp. 151-179.

    Google Scholar 

  • Story MT (1995) Regulation of prostate growth by fibroblast growth factors. World J Urol 13: 297-305.

    Google Scholar 

  • Taraboletti G, Belotti D, Borsotti P, Vergani V, Rusnati M, Presta M, Giavazzi R. (1997) The 140-kilodalton antiangiogenic fragment of thrombospondin-1 binds to basic fibroblast growth factor. Cell Gr Diff 8: 471-479.

    Google Scholar 

  • Tenniswood M (1986) Role of epithelial-stromal interactions in the control of gene expression in the prostate: an hypothesis. Prostate 9: 375-382.

    Google Scholar 

  • Tenniswood M (1997) Apoptosis, tumor invasion and prostate cancer. Br J Urol 79(Suppl. 2): 27-34.

    Google Scholar 

  • Tenover JL (1999) Testosterone replacement therapy in older adult men. Int J Androl 22: 300-306.

    Google Scholar 

  • Wright JA, Huang A (1996) Growth factors in mechanisms of malignancy: roles for TGF-beta and FGF. Histol Histopathol 11: 521-536.

    Google Scholar 

  • Yang E, Moses H (1990) Transforming growth factor beta1-induced changes in cell migration, proliferation and angiogenesis in the chicken chorioallantoic membrane. Prostate 111: 731-739.

    Google Scholar 

  • Zhang J, Lo C (1995) Regulation of fibronectin expression by PDGF-BB and IGF-I in cultured rat thoracic aortic adventitial fibroblasts. Cell Biol Int 19: 517-525.

    Google Scholar 

  • Zhang X, Shu MA, Harvey MB, Schultz GA (1996) Regulation of urokinase plasminogen activator production in implanting mouse embyro: effect of embryo interaction with extracellular matrix. Biol Reprod 54: 1052-1058.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute for Biomedical Research and Department of Anatomy and Histology F13, The University of Sydney, Sydney, NSW, 2006, Australia

    M. Slater, J.A. Barden & C.R. Murphy

Authors
  1. M. Slater
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J.A. Barden
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C.R. Murphy
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Slater, M., Barden, J. & Murphy, C. Changes in Growth Factor Expression in the Ageing Prostate may Disrupt Epithelial–Stromal Homeostasis. Histochem J 32, 357–364 (2000). https://doi.org/10.1023/A:1004065630631

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1004065630631

Keywords

Search

Navigation