Steroid hormone transforming aldo-keto reductases and cancer

Ann N Y Acad Sci. 2009 Feb;1155:33-42. doi: 10.1111/j.1749-6632.2009.03700.x.

Abstract

Prostate and breast cancer are hormone-dependent malignancies of the aging male and female and require the local production of androgens and estrogens to stimulate cell proliferation. Aldo-keto reductases (AKR) play key roles in this process. In the prostate, AKR1C3 (type 5 17beta-HSD) reduces Delta(4)-androstene-3,17-dione to yield testosterone while AKR1C2 (type 3 3alpha-HSD) eliminates 5alpha-dihydrotestosterone (5alpha-DHT), and AKR1C1 forms 3beta-androstanediol (a ligand for ERbeta). In the breast, AKR1C3 forms testosterone, which is converted to 17beta-estradiol by aromatase or reduces estrone to 17beta-estradiol directly. AKR1C3 also acts as a prostaglandin (PG) F synthase and forms PGF(2alpha) and 11beta-PGF(2alpha), which stimulate the FP receptor and prevent the activation of PPARgamma by PGJ(2) ligands. This proproliferative signaling may stimulate the growth of hormone-dependent and -independent prostate and breast cancer.

Publication types

  • Review

MeSH terms

  • Alcohol Oxidoreductases / antagonists & inhibitors
  • Alcohol Oxidoreductases / genetics
  • Alcohol Oxidoreductases / metabolism*
  • Aldehyde Reductase
  • Aldo-Keto Reductases
  • Androgens / metabolism*
  • Breast / enzymology
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / metabolism
  • Chromosome Mapping
  • Enzyme Inhibitors / pharmacology
  • Estrogens / metabolism*
  • Female
  • Humans
  • Hydroxyprostaglandin Dehydrogenases / metabolism
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Male
  • Prostate / enzymology
  • Prostatic Neoplasms / enzymology*
  • Prostatic Neoplasms / metabolism

Substances

  • Androgens
  • Enzyme Inhibitors
  • Estrogens
  • Isoenzymes
  • Alcohol Oxidoreductases
  • Aldo-Keto Reductases
  • Hydroxyprostaglandin Dehydrogenases
  • prostaglandin-F synthase
  • Aldehyde Reductase