CTCF and BORIS Regulate Rb2/p130 Gene Transcription: A Novel Mechanism and a New Paradigm for Understanding the Biology of Lung Cancer

Antonio Russo, Fabrizio Miranda, Antonio Russo, Marcella Macaluso, Francesco Paolo Fiorentino, Luigi Bagella, Luigi Bagella, Antonio Giordano, Micaela Montanari

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29 Citazioni (Scopus)

Abstract

Although innumerable investigations regarding the biology of lung cancer have been carried out, manyaspects thereof remain to be addressed, including the role played by the retinoblastoma-related protein Rb2/p130 during the evolution of this disease. Here we report novel findings on the mechanisms that control Rb2/p130 gene expression in lung fibroblasts and characterize the effects of Rb2/p130 deregulation on theproliferative features of lung cancer cells.We revealed for the first time that in lung fibroblasts the expression ofRb2/p130 gene is directly controlled by the chromatin insulator CCCTC-binding factor, CTCF, which bybinding to the Rb2/p130 gene promoter induces, and/or maintains, a specific local chromatin organization thatin turn governs the transcriptional activity of Rb2/p130 gene. However, in lung cancer cells the activity ofCTCF in controlling Rb2/p130 gene expression is impaired by BORIS, a CTCF-paralogue, which by bindingto the Rb2/p130 gene could trigger changes in the chromatin asset established by CTCF, thereby affectingCTCF regulatory activity on Rb2/p130 transcription. These studies not only provide essential basic insightsinto the molecular mechanisms that control Rb2/p130 gene expression in lung cancer, but also offer a potentialparadigm for the actions of other activators and/or corepressors, such as CTCF and BORIS, that could becrucial in explaining how alterations in the mechanism regulating Rb2/p130 gene expression may acceleratethe progression of lung tumors, or favor the onset of recurrence after cancer treatment. Mol Cancer Res; 9(2);225–33. 2011 AACR.
Lingua originaleEnglish
pagine (da-a)225-233
Numero di pagine9
RivistaMolecular Cancer Research
Volume9
Stato di pubblicazionePublished - 2011

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Oncology
  • Cancer Research

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    Russo, A., Miranda, F., Russo, A., Macaluso, M., Fiorentino, F. P., Bagella, L., Bagella, L., Giordano, A., & Montanari, M. (2011). CTCF and BORIS Regulate Rb2/p130 Gene Transcription: A Novel Mechanism and a New Paradigm for Understanding the Biology of Lung Cancer. Molecular Cancer Research, 9, 225-233.