SHBG is an important factor in stemness induction of cells by DHT in vitro and associated with poor clinical features of prostate carcinomas.
Androgen plays a vital role in prostate cancer development. However, it is not clear whether androgens influence stem-like properties of prostate cancer, a feature important for prostate cancer progression. In this study, we show that upon DHT treatment in vitro, prostate cancer cell lines LNCaP and PC-3 were revealed with higher clonogenic potential and higher expression levels of stemness related factors CD44, CD90, Oct3/4 and Nanog. Moreover, sex hormone binding globulin (SHBG) was also simultaneously upregulated in these cells. When the SHBG gene was blocked by SHBG siRNA knock-down, the induction of Oct3/4, Nanog, CD44 and CD90 by DHT was also correspondingly blocked in these cells. Immunohistochemical evaluation of clinical samples disclosed weakly positive, and areas negative for SHBG expression in the benign prostate tissues, while most of the prostate carcinomas were strongly positive for SHBG. In addition, higher levels of SHBG expression were significantly associated with higher Gleason score, more seminal vesicle invasions and lymph node metastases. Collectively, our results show a role of SHBG in upregulating stemness of prostate cancer cells upon DHT exposure in vitro, and SHBG expression in prostate cancer samples is significantly associated with poor clinicopathological features, indicating a role of SHBG in prostate cancer progression.
Department of Pathology, The Norwegian Radium Hospital, Institute of Clinical Medicine, Oslo University Hospital, Faculty of Medicine, University of Oslo, Oslo, Norway.
Yuanyuan
Y
Ma
Dongming
D
Liang
Jian
J
Liu
Jian-Guo
JG
Wen
Einar
E
Servoll
Gudmund
G
Waaler
Thorstein
T
Sæter
Karol
K
Axcrona
Ljiljana
L
Vlatkovic
Ulrika
U
Axcrona
Elisabeth
E
Paus
Yue
Y
Yang
Zhiqian
Z
Zhang
Gunnar
G
Kvalheim
Jahn M
JM
Nesland
Zhenhe
Z
Suo
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D013196:Dihydrotestosterone / Q000494:pharmacology*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071317:Nanog Homeobox Protein; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D010641:Phenotype; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D012738:Sex Hormone-Binding Globulin / Q000235:genetics / Q000378:metabolism*; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D015415:Biomarkers; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D011944:Receptors, Androgen; D012738:Sex Hormone-Binding Globulin; D013196:Dihydrotestosterone; D017430:Prostate-Specific Antigen