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Related Experiment Videos

Estrogenic effects on prostatic differentiation and carcinogenesis.

G R Cunha1, Y Z Wang, S W Hayward

  • 1Department of Anatomy, University of California, San Francisco 94143, USA.

Reproduction, Fertility, and Development
|January 22, 2002
PubMed
Summary
This summary is machine-generated.

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Estrogen receptors alpha (ERalpha) in both prostate epithelium and stroma are essential for hormone-induced squamous metaplasia. Loss of the Rb tumor suppressor gene predisposes prostate cells to hormonal carcinogenesis, leading to invasive carcinoma.

Area of Science:

  • Endocrinology
  • Prostate Cancer Research
  • Molecular Biology

Background:

  • Estrogens and androgens can drive abnormal prostate growth and malignancy.
  • Estrogen receptors (ER) mediate estrogenic effects in the prostate.
  • Estrogen receptor alpha (ERalpha) is implicated in prostatic squamous metaplasia.

Purpose of the Study:

  • To investigate the specific roles of epithelial and stromal ERalpha in mediating estrogen-induced prostatic squamous metaplasia.
  • To explore the role of the retinoblastoma (Rb) tumor suppressor gene in hormonal carcinogenesis of the prostate.

Main Methods:

  • Construction and analysis of tissue recombinants using wild-type and ERalpha knockout (alphaERKO) mouse prostate epithelium and stroma.
  • Hormonal induction of squamous metaplasia using diethylstilbestrol (DES).

Related Experiment Videos

  • Utilizing a mouse model with rat urogenital sinus mesenchyme and retinoblastoma gene knockout (Rb-KO) prostate epithelium for carcinogenesis studies.

    • Main Results:

    • Full squamous metaplasia required ERalpha in both prostate epithelium and stroma; absence in either prevented response to DES.
    • Tissue recombinants with alphaERKO components failed to exhibit metaplasia.
    • Rb-KO prostate epithelium, when combined with rat urogenital mesenchyme and treated with testosterone and estradiol, efficiently developed hyperplasia, atypical hyperplasia, and invasive carcinoma.
    • During carcinogenesis, E-cadherin decreased, PCNA labeling increased, and smooth muscle cells were lost from the stroma.

    Conclusions:

    • ERalpha is critical in both prostate epithelial and stromal compartments for mediating estrogen-induced squamous metaplasia.
    • The absence of the Rb tumor suppressor gene significantly predisposes prostate epithelial cells to hormonal carcinogenesis.
    • Hormonal carcinogenesis involves specific molecular and cellular changes within the prostate microenvironment.