Transforming growth factor-beta expression in prostate neoplasia

Anal Quant Cytol Histol. 2000 Feb;22(1):1-10.

Abstract

Objective: To understand the role of transforming growth factor (TGF) -beta 1, -beta 2 and -beta 3 proteins and TGF-beta type I and II receptors in prostate neoplasia; to determine the correlation between expression of TGF-beta s and their relative receptors in the epithelial and stromal compartments of benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostate carcinoma; and to determine whether TGF-beta and TGF-beta receptor expression is associated with the grade of tumor differentiation.

Study design: Sixty prostate neoplasms were analyzed by immunohistochemistry using anti-TGF-beta 1, -beta 2, -beta 3, -beta RI and -beta RII antibodies.

Results: TGF-beta and TGF-beta receptor immunoreactivity was more strongly expressed in prostate carcinoma than in PIN and BPH, and TGF-beta type I and type II receptors were less strongly expressed than TGF-beta 1-3 proteins. The difference between epithelial and stromal compartments reached significance (P < .05) for all TGF-beta isoforms and related receptors only in BPH, whereas a significant difference was found for TGF-beta protein in all grades of PIN but not for prostate carcinoma tissue. Luminal epithelial cells of BPH and PIN coexpressed all three TGF-beta isoforms and preferentially TGF-beta RII. Conversely, basal epithelial cells stained strongly for TGF-beta 1, -beta 3 and -beta RI but not for TGF-beta 2 and more strongly for TGF-beta RI than -beta RII. Linear regression showed a positive correlation between TGF-beta 1 and -beta 2, between TGF-beta 2 and -beta 3 and between TGF-beta RI and -beta RII proteins in all areas. The epithelium of Gleason score 7 tumors contained significantly higher TGF-beta 2 protein levels than Gleason score 3 and 4, and 5 and 6 tumors (P < .05).

Conclusion: Stromal and epithelial cells of malignant and nonmalignant prostatic tumors express all three TGF-beta isoforms and their related receptors. These may act as both paracrine and autocrine factors to influence prostate function and the stromal-epithelial cell interaction. TGF-beta and -beta R immunoreactivity noted in basal cells indicates that in BPH and PIN, TGF-beta Rs and signaling pathways remain intact. The overexpression of TGF-beta proteins and underexpression of TGF-beta receptors in prostate cancer could suggest a mechanism for prostate cancer cells to escape the growth inhibitory effect of TGF-beta, thus leading to a more malignant phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors, Type I*
  • Aged
  • Aged, 80 and over
  • Biomarkers / analysis
  • Epithelial Cells / chemistry
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Prostatic Hyperplasia / metabolism
  • Prostatic Intraepithelial Neoplasia / chemistry
  • Prostatic Intraepithelial Neoplasia / metabolism
  • Prostatic Neoplasms / chemistry
  • Prostatic Neoplasms / metabolism*
  • Protein Isoforms
  • Protein-Serine-Threonine Kinases / biosynthesis
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / biosynthesis
  • Stromal Cells / chemistry
  • Transforming Growth Factor beta / biosynthesis*
  • Transforming Growth Factor beta / immunology

Substances

  • Biomarkers
  • Protein Isoforms
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Protein-Serine-Threonine Kinases
  • Activin Receptors, Type I
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II