SHBG is an important factor in stemness induction of cells by DHT in vitro and associated with poor clinical features of prostate carcinomas
Authors: Ulrika Axcrona
Jian Liu
Ljiljana Vlatkovic
Jian-Guo Wen
Yue Yang
Jahn M Nesland
Dongming Liang
Karol Axcrona
Elisabeth Paus
Einar Servoll
Yuanyuan Ma
Zhenhe Suo
Thorstein S√¶ter
Gunnar Kvalheim
Gudmund Waaler
Zhiqian Zhang
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Androgen; Prostate cancer; Stem-like properties; DHT treatment; Clonogenic potential
Affiliations: 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. 

Retracted: Yes

PubPeer comments:
 WB bands in Fig.3A of differently treated samples and of proteins with distinct molecular weight are actually the same, just with various exposure time. # **Fig.3A**  , 
 Immunocytochemistry photos from different cell lines in Fig.5A are the same. # **Fig.5A**  , 
 Same loading control used for two different cell lines:  , 
 2020 retraction. https: journals.plos.org plosone article?id=10.1371 journal.pone.0237487 Following the publication of this article [1], concerns have been raised regarding the immunoblotting data presented in Fig 3A as well as the immunocytochemistry data presented in Fig 5A. Specifically, In Fig 3A, the bands in Oct3 4 panel 10 nM DHT treated LNCaP cells (lanes 9u201312) appear similar to the bands in Nanog panel 0 nM DHT treated LNCaP cells (lanes 1u20134). In Fig 3A, the bands in GADPH panel 1 nM DHT treated LNCaP cells (lanes 5u20138) appear similar to the bands in GADPH panel 1nM DHT treated PC-3 cells (lanes 5u20138). In Fig 5A, the panel representing immunocytochemical staining of 0 nM DHT treated LNCaP cells appears similar to the panel representing immunocytochemical staining of 0 nM DHT treated PC-3 cells. The Commission on Research Integrity at Oslo University Hospital and Institute of Clinical Medicine, University of Oslo completed an investigation and confirmed the concerns with Fig 3A and Fig 5A. The authors indicated that the wrong images have been uploaded for the Nanog panel of the 0 nM DHT treated LNCaP cells, and the GAPDH panel of the 1 nM DHT treated PC-3 cells presented in Fig 3A. Furthermore, the authors indicated that the wrong images have been used for the 0 nM DHT treated LNCaP and PC-3 cells presented in Fig 5A. The authors offered replacement images for the panels of concern and provided supporting data for some of the results reported in the article. However, data were not provided in support of all panels for the experiments in question, and discrepancies were noted between the supporting image provided and the published figure for the Nanog panel of the 0 nM DHT treated PC-3 cells in Fig 3A. Overall, the data and information provided by the authors have not fully resolved the concerns. Given the remaining issues for Fig 3A and the data shown in the figure, the articleu2019s claims based on the western blot results in this figure are not adequately supported. In light of the above concerns and in line with the institutionu2019s recommendation, the PLOS ONE Editors retract this article. GW, KA, UA, and ZZ agreed with the retraction. DL and ZS did not confirm agreement or disagreement with the retraction decision. YM, JGW, ES, TS, LV, EP, YY, GK, and JMN either did not respond directly or could not be reached. JL did not agree with the retraction. Reference 1.Ma Y, Liang D, Liu J, Wen J-G, Servoll E, Waaler G, et al. (2013) 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 8(7): e70558. https: doi.org 10.1371 journal.pone.0070558 ,