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Related Experiment Videos

Local aromatase expression in human prostate is altered in malignancy.

Stuart J Ellem1, Jacqueline F Schmitt, John S Pedersen

  • 1Centre for Urological Research, Monash Institute of Reproduction and Development, Clayton, Victoria 3168, Australia.

The Journal of Clinical Endocrinology and Metabolism
|May 6, 2004
PubMed
Summary

Local estrogen production via aromatase occurs in the prostate, particularly in malignant tissues. This finding suggests a potential role for local estrogen biosynthesis in prostate disease progression.

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Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Tissue-specific aromatase production is crucial in breast cancer and osteoporosis.
  • Prostatic aromatase expression and local estrogen actions have been unclear, often considered secondary to systemic androgen suppression.

Purpose of the Study:

  • To investigate local aromatase expression and estrogen biosynthesis within the human prostate.
  • To determine the cellular localization and activity of aromatase in both normal and malignant prostate tissues.

Main Methods:

  • Laser capture microdissection to isolate pure stromal and epithelial cells from biopsy tissues.
  • Detection of aromatase protein (Western blot), mRNA (RT-PCR), and enzyme activity (tritiated water assay).
  • Real-time PCR was used to examine aromatase promoter utilization.

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Main Results:

  • In nonmalignant prostate tissues, aromatase mRNA and protein were localized to the stroma, driven by promoter PII; epithelial cells showed no expression.
  • Aromatase was expressed and enzymatically active in prostate cancer cell lines (LNCaP, PC3, DU145) and microdissected tumor epithelial cells.
  • Prostate cancer cells utilized different promoters (PII in LNCaP, I.4 in PC3 and DU145), indicating altered promoter use with malignancy.

Conclusions:

  • This study demonstrates local estrogen biosynthesis in the human prostate.
  • Aromatase gene expression in prostate malignancy is induced locally.
  • Altered aromatase promoter use in cancer suggests a role for local estrogen production in prostate disease progression.