title: Heightened expression of CTCF in breast cancer cells is associated with resistance to apoptosis.
abstract: CTCF is a candidate tumor suppressor gene encoding a multifunctional transcription factor. Surprisingly for a tumor suppressor, the levels of CTCF in breast cancer cell lines and tumors were found elevated compared with breast cell lines with finite life span and normal breast tissues. In this study, we aimed to investigate the possible cause for this increase in CTCF content and in particular to test the hypothesis that up-regulation of CTCF may be linked to resistance of breast cancer cells to apoptosis. For this purpose, apoptotic cell death was monitored following alterations of CTCF levels induced by transient transfection and conditional knockdown of CTCF in various cell lines. We observed apoptotic cell death in all breast cancer cell lines examined following CTCF down-regulation. In addition, overexpression of CTCF partially protected cells from apoptosis induced by overexpression of Bax or treatment with sodium butyrate. To elucidate possible mechanisms of this phenomenon, we used a proteomics approach and observed that levels of the proapoptotic protein, Bax, were increased following CTCF down-regulation in MCF7 cells. Taken together, these results suggest that in some cellular contexts CTCF shows antiapoptotic characteristics, most likely exerting its functions through regulation of apoptotic genes. We hypothesize that CTCF overexpression may have evolved as a compensatory mechanism to protect breast cancer cells from apoptosis, thus providing selective survival advantages to these cells. The observations reported in this study may lead to development of therapies based on selective reduction of CTCF in breast cancer cells.
authors.affiliation: Department of Biological Sciences, Central Campus, University of Essex, Essex, United Kingdon.
authors.forename: France
authors.initials: F
authors.lastname: Docquier
authors.forename: Dawn
authors.initials: D
authors.lastname: Farrar
authors.forename: Vivien
authors.initials: V
authors.lastname: D'Arcy
authors.forename: Igor
authors.initials: I
authors.lastname: Chernukhin
authors.forename: Abigail F
authors.initials: AF
authors.lastname: Robinson
authors.forename: Dmitry
authors.initials: D
authors.lastname: Loukinov
authors.forename: Sergei
authors.initials: S
authors.lastname: Vatolin
authors.forename: Svetlana
authors.initials: S
authors.lastname: Pack
authors.forename: Alan
authors.initials: A
authors.lastname: Mackay
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harris
authors.forename: Heather
authors.initials: H
authors.lastname: Dorricott
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Hare
authors.forename: Victor
authors.initials: V
authors.lastname: Lobanenkov
authors.forename: Elena
authors.initials: E
authors.lastname: Klenova
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000076246:CCCTC-Binding Factor; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012097:Repressor Proteins; D051028:bcl-2-Associated X Protein