title: Decreased poly(ADP-ribosyl)ation of CTCF, a transcription factor, is associated with breast cancer phenotype and cell proliferation.
abstract: OBJECTIVE
  There is compelling evidence of a relationship between poly(ADP-ribosyl)ation and tumorigenesis; however, much less is known about the role of specific targets of poly(ADP-ribosyl)ation in tumor development. Two forms of the multifunctional transcription factor, CTCF, were previously identified: a 130-kDa protein (CTCF-130), characteristic for cell lines, and a 180-kDa protein (CTCF-180), modified by poly(ADP-ribosyl)ation. This study was aimed to investigate differential poly(ADP-ribosyl)ation of CTCF in normal and tumor breast tissues.
  
  
  METHODS
  Western blot analysis, mass spectrometry, and immunohistochemical and immunofluorescent stainings were used to characterize CTCF-130 and CTCF-180 in breast cell lines, primary cultures, and normal and tumor breast tissues. The immunoreactivity score was used for CTCF-130 quantification in tissues.
  
  
  RESULTS
  We discovered that only CTCF-180 is detected in the normal breast tissues, whereas both CTCF-130 and CTCF-180 are present in breast tumors. Using an antibody specific for CTCF-130, we observed that 87.7% of breast tumors were positive for CTCF-130. A negative correlation existed between the levels of CTCF-130, tumor stage, and tumor size. Significantly, a transition from CTCF-180 to CTCF-130 was discovered in primary cultures generated from normal breast tissues, indicating a link between CTCF-130 and proliferation. Conversely, the appearance of CTCF-180 was observed following growth arrest in breast cell lines.
  
  
  CONCLUSIONS
  Collectively, our data suggest that the loss of CTCF poly(ADP-ribosyl)ation is associated with cell proliferation and breast tumor development. We propose the use of CTCF-130 as a marker for tumor breast cells and lower levels of CTCF-130 as an indicator of unfavorable prognosis.
authors.affiliation: Department of Biological Sciences, University of Essex, Essex, United Kingdom.
authors.forename: France
authors.initials: F
authors.lastname: Docquier
authors.forename: Georgia-Xanthi
authors.initials: GX
authors.lastname: Kita
authors.forename: Dawn
authors.initials: D
authors.lastname: Farrar
authors.forename: Parmjit
authors.initials: P
authors.lastname: Jat
authors.forename: Michael
authors.initials: M
authors.lastname: O'Hare
authors.forename: Igor
authors.initials: I
authors.lastname: Chernukhin
authors.forename: Svetlana
authors.initials: S
authors.lastname: Gretton
authors.forename: Adhip
authors.initials: A
authors.lastname: Mandal
authors.forename: Louise
authors.initials: L
authors.lastname: Alldridge
authors.forename: Elena
authors.initials: E
authors.lastname: Klenova
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D000076246:CCCTC-Binding Factor; D049109:Cell Proliferation; D006801:Humans; D010641:Phenotype; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D012097:Repressor Proteins; D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases