SHBG is an important factor in stemness induction of cells by DHT in vitro and associated with poor clinical features of prostate carcinomas

Yuanyuan Ma; Dongming Liang; Jian Liu; Jian-Guo Wen; Einar Servoll; Gudmund Waaler; Thorstein Sæter; Karol Axcrona; Ljiljana Vlatkovic; Ulrika Axcrona; Elisabeth Paus; Yue Yang; Zhiqian Zhang; Gunnar Kvalheim; Jahn M Nesland; Zhenhe Suo

doi:10.1371/journal.pone.0070558

SHBG is an important factor in stemness induction of cells by DHT in vitro and associated with poor clinical features of prostate carcinomas

PLoS One. 2013 Jul 30;8(7):e70558. doi: 10.1371/journal.pone.0070558. Print 2013.

Authors

Yuanyuan Ma¹, Dongming Liang, Jian Liu, Jian-Guo Wen, Einar Servoll, Gudmund Waaler, Thorstein Sæter, Karol Axcrona, Ljiljana Vlatkovic, Ulrika Axcrona, Elisabeth Paus, Yue Yang, Zhiqian Zhang, Gunnar Kvalheim, Jahn M Nesland, Zhenhe Suo

Affiliation

¹ Department of Pathology, The Norwegian Radium Hospital, Institute of Clinical Medicine, Oslo University Hospital, Faculty of Medicine, University of Oslo, Oslo, Norway.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't
Retracted Publication

MeSH terms

Adult
Aged
Biomarkers / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects
Dihydrotestosterone / pharmacology*
Disease Progression
Gene Expression Regulation, Neoplastic / drug effects
Homeodomain Proteins / metabolism
Humans
Male
Middle Aged
Nanog Homeobox Protein
Neoplasm Grading
Neoplasm Staging
Neoplastic Stem Cells / drug effects*
Neoplastic Stem Cells / metabolism*
Octamer Transcription Factor-3 / metabolism
Phenotype
Prognosis
Prostate-Specific Antigen / metabolism
Prostatic Neoplasms / genetics
Prostatic Neoplasms / metabolism*
Prostatic Neoplasms / pathology*
Receptors, Androgen / genetics
Receptors, Androgen / metabolism
Sex Hormone-Binding Globulin / genetics
Sex Hormone-Binding Globulin / metabolism*
Spheroids, Cellular
Tumor Cells, Cultured
Tumor Stem Cell Assay

Substances

Biomarkers
Homeodomain Proteins
NANOG protein, human
Nanog Homeobox Protein
Octamer Transcription Factor-3
Receptors, Androgen
Sex Hormone-Binding Globulin
Dihydrotestosterone
Prostate-Specific Antigen

Grants and funding

This work is supported by the The Norwegian Radium Hospital Research Foundation and National Natural Science Foundation of China, grant no 81272824. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.