Prostate cancer cell lines under hypoxia exhibit greater stem-like properties
Authors: Dongming Liang
Karol Axcrona
Jian Liu
Yuanyuan Ma
Zhenhe Suo
Gunnar Kvalheim
Trond Stokke
Jahn M Nesland
Journal: PLoS ONE (2011)
Discipline: Multidisciplinary
Keywords: Hypoxia; Cancer stem cells; Prostate cancer; HIF-1Œ±; HIF-2Œ±
Affiliations: Department of Pathology, University of Oslo, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.

Abstract:  Hypoxia is an important environmental change in many cancers. Hypoxic niches can be occupied by cancer stem/progenitor-like cells that are associated with tumor progression and resistance to radiotherapy and chemotherapy. However, it has not yet been fully elucidated how hypoxia influences the stem-like properties of prostate cancer cells. In this report, we investigated the effects of hypoxia on human prostate cancer cell lines, PC-3 and DU145. In comparison to normoxia (20% O(2)), 7% O(2) induced higher expressions of HIF-1Œ± and HIF-2Œ±, which were associated with upregulation of Oct3/4 and Nanog; 1% O(2) induced even greater levels of these factors. The upregulated NANOG mRNA expression in hypoxia was confirmed to be predominantly retrogene NANOGP8. Similar growth rates were observed for cells cultivated under hypoxic and normoxic conditions for 48 hours; however, the colony formation assay revealed that 48 hours of hypoxic pretreatment resulted in the formation of more colonies. Treatment with 1% O(2) also extended the G(0)/G(1) stage, resulting in more side population cells, and induced CD44 and ABCG2 expressions. Hypoxia also increased the number of cells positive for ABCG2 expression, which were predominantly found to be CD44(bright) cells. Correspondingly, the sorted CD44(bright) cells expressed higher levels of ABCG2, Oct3/4, and Nanog than CD44(dim) cells, and hypoxic pretreatment significantly increased the expressions of these factors. CD44(bright) cells under normoxia formed significantly more colonies and spheres compared with the CD44(dim) cells, and hypoxic pretreatment even increased this effect. Our data indicate that prostate cancer cells under hypoxia possess greater stem-like properties. 

Retracted: Yes

PubPeer comments:
 RT-PCR bands in Fig.2A are the same, just with changes of brightness contrast. # **Fig.2A**  , 
 Immunocytochemistry photos from different cell lines in Fig.2B are the same. # **Fig.2B**  , 
 2020 retraction. https: journals.plos.org plosone article?id=10.1371 journal.pone.0233203 Following the publication of this article [1], concerns have been raised regarding the RT-PCR data presented in Fig 2A and the immunochemistry data presented in Fig 2B: Fig 2A RT-PCR, the bands in the Nanog panel 1% O2 treated PC-3 cells (lanes 1u20134) appear similar to the bands in the Nanog panel 7% O2 treated DU145 cells (lanes 5u20138). Fig 2A RT-PCR, the bands in the Nanog panel 20% O2 treated PC-3 cells (lanes 1u20134) appear similar to the bands in the Nanog panel 20% O2 treated DU145 cells (lanes 5u20138). Fig 2A RT-PCR, the bands in the GAPDH panel 1% O2 treated PC-3 cells (lanes 1u20134) appear similar to the bands in the GAPDH panel 20% O2 treated DU145 cells (lanes 5u20138). Fig 2B, the immunocytochemistry image of Nanog panel 20% O2 treated PC-3 cells appears similar to the immunocytochemistry image of Nanog panel 20% O2 treated DU145 cells. The Commission on Research Integrity at Oslo University Hospital and Institute of Clinical Medicine, University of Oslo completed an investigation and concluded that there was evidence of scientific misconduct in the case of Fig 2A, and negligence in the preparation of Fig 2B. In light of the above concerns and in line with the institutionu2019s recommendation, the PLOS ONE Editors retract this article. YM, DL, JL, GK, and JMN did not respond. KA and TS agreed with the retraction. ZS did not agree with the retraction. References 1.Ma Y, Liang D, Liu J, Axcrona K, Kvalheim G, Stokke T, et al. (2011) Prostate Cancer Cell Lines under Hypoxia Exhibit Greater Stem-Like Properties. PLoS ONE 6(12): e29170. https: doi.org 10.1371 journal.pone.0029170 ,