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.

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

Grant support

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.