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Steroid Hormone Transforming Aldo‐Keto Reductases and Cancer
Author(s) -
Penning Trevor M.,
Byrns Michael C.
Publication year - 2009
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2009.03700.x
Subject(s) - aromatase , medicine , testosterone (patch) , endocrinology , estrone , dihydrotestosterone , prostate cancer , receptor , androgen receptor , hormone , chemistry , androgen , cancer , cancer research , breast cancer , biology
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 Δ 4 ‐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 PGF 2α and 11β‐PGF 2α , which stimulate the FP receptor and prevent the activation of PPARγ by PGJ 2 ligands. This proproliferative signaling may stimulate the growth of hormone‐dependent and ‐independent prostate and breast cancer.