Evidence for steroidogenic potential in human prostate cell lines and tissues.
Malignant prostate cancer (PCa) is usually treated with androgen deprivation therapies (ADTs). Recurrent PCa is resistant to ADT. This research investigated whether PCa can potentially produce androgens de novo, making them androgen self-sufficient. Steroidogenic enzymes required for androgen synthesis from cholesterol (CYP11A1, CYP17A1, HSD3β, HSD17β3) were investigated in human primary PCa (n = 90), lymph node metastases (LNMs; n = 8), and benign prostatic hyperplasia (BPH; n = 6) with the use of IHC. Six prostate cell lines were investigated for mRNA and protein for steroidogenic enzymes and for endogenous synthesis of testosterone and 5α-dihydrotestosterone. All enzymes were identified in PCa, LNMs, BPH, and cell lines. CYP11A1 (rate-limiting enzyme) was expressed in cancerous and noncancerous prostate glands. CYP11A1, CYP17A1, HSD3β, and HSD17β3 were identified, respectively, in 78%, 52%, 16%, and 82% of human BPH and PCa samples. Approximately 10% of primary PCa, LNMs, and BPH expressed all four enzymes simultaneously. CYP11A1 expression was stable, CYP17A1 increased, and HSD3β and HSD17β3 decreased with disease progression. CYP17A1 expression was significantly correlated with CYP11A1 (P = 0.0009), HSD3β (P = 0.0297), and HSD17β3 (P = 0.0090) in vivo, suggesting CYP17A1 has a key role in prostatic steroidogenesis similar to testis and adrenal roles. In vitro, all cell lines expressed mRNA for all enzymes. Protein was not always detectable; however, all cell lines synthesized androgen from cholesterol. The results indicate that monitoring steroidogenic metabolites in patients with PCa may provide useful information for therapy intervention.
School of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia.
Nigel C
NC
Bennett
John D
JD
Hooper
Duncan
D
Lambie
Cheok S
CS
Lee
Tao
T
Yang
David A
DA
Vesey
Hemamali
H
Samaratunga
David W
DW
Johnson
Glenda C
GC
Gobe
D000728:Androgens / Q000096:biosynthesis; D045744:Cell Line, Tumor; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D016014:Linear Models; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D011467:Prostate / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*
D000728:Androgens; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D013256:Steroids