Level of FACT defines the transcriptional landscape and aggressive phenotype of breast cancer cells.

作者: Daria Fleyshman , Laura Prendergast , Alfiya Safina , Geraldine Paszkiewicz , Mairead Commane

DOI: 10.18632/ONCOTARGET.15656

关键词: DNA replicationBreast cancerGeneSmall hairpin RNABiologyTranscription (biology)Cell cycleHistonePhenotypeCancer researchGenetics

摘要: // Daria Fleyshman 1 , Laura Prendergast Alfiya Safina Geraldine Paszkiewicz Mairead Commane Kelsey Morgan Kristopher Attwood 1,2 and Katerina Gurova Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA 2 Biostatistics, University SUNY, Correspondence to: Gurova, email: Keywords : FACT, SSRP1, SPT16, curaxin CBL0137, breast cancer Received December 29, 2016 Accepted January 11, 2017 Published February 23, Abstract Although (BrCa) may be detected at an early stage, there is a shortage markers that predict tumor aggressiveness lack targeted therapies. Histone chaperone expressed in limited number normal cells, overexpressed different types cancer, including BrCa. Recently, we found FACT expression BrCa correlates with aggressive BrCa, which prompted us to explore the consequences inhibition cells varying levels FACT. using small molecule or shRNA caused reduced growth viability all tested. Phenotypic changes were more severe “high- FACT” (death arrest) than “low-FACT” (decreased proliferation). Though had no effect on rate general transcription, individual genes was changed cell-specific manner. Initially distinct transcriptional profiles became similar upon equalizing expression. In “high-FACT” supports involved regulation cell cycle, DNA replication, maintenance undifferentiated state regulated by activity several proto-oncogenes. presence reduces encoding enzymes steroid metabolism are characteristic differentiated mammary epithelia. Thus, propose both marker target whose results death convertion them less subtype.

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