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.
|Numero di pagine||9|
|Rivista||Molecular Cancer Research|
|Stato di pubblicazione||Published - 2011|
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