Decreased poly(ADP-ribosyl)ation of CTCF, a transcription factor, is associated with breast cancer phenotype and cell proliferation
| Autor: | France Docquier, Georgia-Xanthi Kita, Dawn Farrar, Parmjit Jat, Michael O'Hare, Igor Chernukhin, Svetlana Gretton, Adhip Mandal, Louise Alldridge, Elena Klenova |
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| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty CCCTC-Binding Factor Poly Adenosine Diphosphate Ribose CA 15-3 Breast Neoplasms Biology medicine.disease_cause Breast cancer medicine Tumor Cells Cultured Humans Transcription factor Cell Proliferation Cell growth Cancer medicine.disease Repressor Proteins Phenotype Oncology CTCF Cancer research Breast disease Poly(ADP-ribose) Polymerases Carcinogenesis |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 15(18) |
| ISSN: | 1557-3265 |
| Popis: | Purpose: 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. Experimental Design: 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. (Clin Cancer Res 2009;15(18):5762–71) |
| Databáze: | OpenAIRE |
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