Steroid Hormone Transforming Aldo-Keto Reductases and Cancer

• Published in: Annals of the New York Academy of Sciences 2009-02, Vol.1155 (1), p.33-42
• Main Authors: Penning, Trevor M., Byrns, Michael C.
• Format: Article
• Language: English
• Subjects: Alcohol Oxidoreductases - antagonists & inhibitors; Alcohol Oxidoreductases - genetics; Alcohol Oxidoreductases - metabolism; Aldehyde Reductase; aldo-keto 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; hydroxysteroid dehydrogenase; Isoenzymes - antagonists & inhibitors; Isoenzymes - genetics; Isoenzymes - metabolism; Male; nonsteroidal anti-inflammatory drugs (NSAIDs); nuclear receptors; prostaglandin F; Prostate - enzymology; Prostatic Neoplasms - enzymology; Prostatic Neoplasms - metabolism
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/j.1749-6632.2009.03700.x

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 17β‐HSD) reduces Δ4‐androstene‐3,17‐dione to yield testosterone while AKR1C2 (type 3 3α‐HSD) eliminates 5α‐dihydrotestosterone (5α‐DHT), and AKR1C1 forms 3β‐androstanediol (a ligand for ERβ). In the breast, AKR1C3 forms testosterone, which is converted to 17β‐estradiol by aromatase or reduces estrone to 17β‐estradiol directly. AKR1C3 also acts as a prostaglandin (PG) F synthase and forms PGF2α and 11β‐PGF2α, which stimulate the FP receptor and prevent the activation of PPARγ by PGJ2 ligands. This proproliferative signaling may stimulate the growth of hormone‐dependent and ‐independent prostate and breast cancer.