Expression of FACT in mammalian tissues suggests its role in maintaining of undifferentiated state of cells
| Autor: | Henry Garcia, Geraldine M. Paszkiewicz, Angela Omelian, Mairead Commane, Katerina Gurova, Alfiya Safina, Carl Morrison, Daria Fleyshman, Katerina Kolesnikova |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Transcription Genetic oncotarget proliferation Fibrosarcoma Cellular differentiation Cell Cycle Proteins Biology SSRP1 Chromatin remodeling chromatin remodeling Myoblasts Mice Transcription (biology) Gene expression cancer Animals Humans Proliferation Marker Transcription factor Cells Cultured Cell Proliferation Cell growth High Mobility Group Proteins Cell Differentiation differentiation Research Papers Chromatin Cell biology DNA-Binding Proteins Ki-67 Antigen Oncology SPT16 Female Transcriptional Elongation Factors transcription Transcription Factors |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | Henry Garcia 1 , Daria Fleyshman 1 , Katerina Kolesnikova 1 , Alfiya Safina 1 , Mairead Commane 1 , Geraldine Paszkiewicz 1 , Angela Omelian 2 , Carl Morrison 2 , Kateryna Gurova 1 1 Department of Cell Stress Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263 2 Department 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. |
| Databáze: | OpenAIRE |
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