High expression of hTERT and stemness genes in BORIS/CTCFL positive cells isolated from embryonic cancer cells

Loredana Alberti; Stéphanie Renaud; Lorena Losi; Serge Leyvraz; Jean Benhattar

doi:10.1371/journal.pone.0109921

High expression of hTERT and stemness genes in BORIS/CTCFL positive cells isolated from embryonic cancer cells

PLoS One. 2014 Oct 3;9(10):e109921. doi: 10.1371/journal.pone.0109921. eCollection 2014.

Authors

Loredana Alberti¹, Stéphanie Renaud², Lorena Losi³, Serge Leyvraz⁴, Jean Benhattar⁵

Affiliations

¹ Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland.
² Institute of Biotechnology, University of Lausanne, Lausanne, Switzerland.
³ Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
⁴ Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland.
⁵ Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland; Biopath Lab, Lausanne, Switzerland.

Abstract

BORIS/CTCFL is a member of cancer testis antigen family normally expressed in germ cells. In tumors, it is aberrantly expressed although its functions are not completely well-defined. To better understand the functions of BORIS in cancer, we selected the embryonic cancer cells as a model. Using a molecular beacon, which specifically targets BORIS mRNA, we demonstrated that BORIS positive cells are a small subpopulation of tumor cells (3-5% of total). The BORIS-positive cells isolated using BORIS-molecular beacon, expressed higher telomerase hTERT, stem cell (NANOG, OCT4, SOX2) and cancer stem cell marker genes (CD44 and ALDH1) compared to the BORIS-negative tumor cells. In order to define the functional role of BORIS, stable BORIS-depleted embryonic cancer cells were generated. BORIS silencing strongly down-regulated the expression of hTERT, stem cell and cancer stem cell marker genes. Moreover, the BORIS knockdown increased cellular senescence in embryonic cancer cells, revealing a putative role of BORIS in the senescence biological program. Our data indicate an association of BORIS expressing cells subpopulation with the expression of stemness genes, highlighting the critical role played by BORIS in embryonic neoplastic disease.

Publication types

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

MeSH terms

Apoptosis
Blotting, Western
Cell Proliferation
DNA Methylation
DNA-Binding Proteins / antagonists & inhibitors
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Embryonic Stem Cells / metabolism*
Embryonic Stem Cells / pathology
Epigenesis, Genetic
Female
Gene Expression Regulation, Neoplastic*
Humans
Molecular Imaging
Neoplastic Stem Cells / metabolism*
Neoplastic Stem Cells / pathology
Ovarian Neoplasms / genetics
Ovarian Neoplasms / metabolism*
Ovarian Neoplasms / pathology
Promoter Regions, Genetic / genetics
RNA, Messenger / genetics
RNA, Small Interfering / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Telomerase / genetics
Telomerase / metabolism*
Tumor Cells, Cultured

Substances

CTCFL protein, human
DNA-Binding Proteins
RNA, Messenger
RNA, Small Interfering
TERT protein, human
Telomerase

Grants and funding

This research was supported by the Swiss National Science Foundation (grant number: 31003A-113505; www.snf.ch); and Emma Muschamp Foundation (www.s-a-v.org/-Fondations-associees-.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.