Oncotarget

Research Papers:

Expression of FACT in mammalian tissues suggests its role in maintaining of undifferentiated state of cells

Henry Garcia, Daria Fleyshman, Katerina Kolesnikova, Alfiya Safina, Mairead Commane, Geraldine Paszkiewicz, Angela Omelian, Carl Morrison & Katerina Gurova _

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Oncotarget. 2011; 2:783-796. https://doi.org/10.18632/oncotarget.340

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Abstract

Henry Garcia1, Daria Fleyshman1, Katerina Kolesnikova1, Alfiya Safina1, Mairead Commane1, Geraldine Paszkiewicz1, Angela Omelian2, Carl Morrison2, Kateryna Gurova1

1Department of Cell Stress Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263

2Department of Pathology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263

Received: October 3, 2011; Accepted: October 11, 2011; Published: October 13, 2011;

Keywords: chromatin remodeling, transcription, SPT16, SSRP1, cancer, differentiation, proliferation, oncotarget

Correspondence:

Katerina Gurova, email:

Abstract

The Facilitates Chromatin Transcription (FACT) chromatin remodeling complex, comprised of two subunits, SSRP1 and SPT16, is involved in transcription, replication and DNA repair. We recently showed that curaxins, small molecules with anti-cancer activity, target FACT and kill tumor cells in a FACT-dependent manner. We also found that FACT is overexpressed in human and mouse tumors and that tumor cells are sensitive to FACT downregulation. To clarify the clinical potential of FACT inhibition, we were interested in physiological role(s) of FACT in multicellular organisms. We analyzed SSRP1 and SPT16 expression in different cells, tissues and conditions using Immunohistochemical (IHC) staining of mouse and human tissues and analysis of publically available high-content gene expression datasets. Both approaches demonstrated coordinated expression of the two FACT subunits, which was primarily associated with the stage of cellular differentiation. Most cells of adult tissues do not have detectable protein level of FACT. High FACT expression was associated with stem or less-differentiated cells, while low FACT levels were seen in more differentiated cells. Experimental manipulation of cell differentiation and proliferation in vitro, as well as tissue staining for the Ki67 proliferation marker, showed that FACT expression is related more to differentiation than to proliferation. Thus, FACT may be part of a stem cell-like gene expression signature and play a role in maintaining cells in an undifferentiated state, which is consistent with its potential role as an anti-cancer target.


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