Five-alpha reductase inhibitor influences expression of androgen receptor and HOXB13 in human hyperplastic prostate tissue.
OBJECTIVE
Five-alpha reductase inhibitors (5ARIs) are known as chemopreventive agents in prostate cancer with a risk of high-grade disease. This study evaluated the effects of 5ARI on androgen receptor (AR) and proteins involved in prostate cell growth such as HOXB13 expression in human prostate tissue and LNCaP prostate cancer cells.


METHODS
We retrospectively selected 21 patients who underwent TURP between March 2007 and February 2010 for previously confirmed BPH by prostate biopsy. They were grouped into control (group 1, n = 9) and 5ARI treatment (group 2, n = 12) before TURP. AR and HOXB13 expression in prostate tissue was evaluated by immunohistochemical staining. We tested the effect of 5ARI on the expression of AR, prostate specific antigen (PSA) and HOXB13 in LNCaP cells. Cells were assessed by Western blot analysis, MTT in vitro proliferation assay, and ELISA.


RESULTS
Group 2 showed stronger reactivity for AR and HOXB13 than those of the group 1. MTT assay showed death of LNCaP cells at 25uM of 5ARI. At the same time, ELISA assay for PSA showed that 5ARI inhibited secretion of PSA in LNCaP cells. Western blot analysis showed that 5ARI did not greatly alter AR expression but it stimulated the expression of HOXB13.


CONCLUSIONS
These results demonstrated that 5ARI influences AR and HOXB13 expression in both LNCaP cells and human prostate tissue. In order to use 5ARI in chemoprevention of prostate cancer, we still need to clarify the influence of 5ARI in ARs and oncogenic proteins and its regulation pathway.
Department of Urology and Department of Anatomy Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, Korea.
Chaeyong
C
Jung
Youngwoong
Y
Park
Young-Rang
YR
Kim
Soo Bang
SB
Ryu
Taek Won
TW
Kang
D058891:5-alpha Reductase Inhibitors / Q000627:therapeutic use*; D000368:Aged; D001378:Azasteroids / Q000627:therapeutic use; D015153:Blotting, Western; D045744:Cell Line, Tumor; D000068538:Dutasteride; D004797:Enzyme-Linked Immunosorbent Assay; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011467:Prostate / Q000737:chemistry / Q000187:drug effects; D017430:Prostate-Specific Antigen / Q000097:blood; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*; D012189:Retrospective Studies; D013997:Time Factors; D014157:Transcription Factors / Q000032:analysis; D014407:Tumor Cells, Cultured
D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; C484414:HOXB13 protein, human; D018398:Homeodomain Proteins; D011944:Receptors, Androgen; D014157:Transcription Factors; D017430:Prostate-Specific Antigen; D000068538:Dutasteride