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999			_c17727 _d17727
003			PC17727
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008			231027b xxu||||| |||| 00| 0 eng d
040			_cH12O
041			_aeng
100			_92805 _aSantos, Mirentxu _eInstituto de Investigación i+12
100			_92806 _aMartínez Fernández, Mónica _eInstituto de Investigación i+12
100			_93370 _aLorz, Corina _eInstituto de Investigación imas12
100			_92814 _aParamio, Jesús M. _eInstituto de Investigación i+12
245	0	0	_aDeregulation of the pRb-E2F4 axis alters epidermal homeostasis and favors tumor development. _h[artículo]
260			_bOncotarget, _c2016
300			_a7(46):75712-28.
500			_aFormato Vancouver: Costa C, Santos M, Martínez Fernández M, Lorz C, Lázaro S, Paramio JM. Deregulation of the pRb-E2F4 axis alters epidermal homeostasis and favors tumor development. Oncotarget. 2016 Nov 15;7(46):75712-28.
501			_aPMID: 27708231 PMC5342772.
504			_aContiene 55 referencias
505			_aErratum in: Oncotarget. 2017 Jul 25;8(30):50324.
520			_aE2F/RB activity is altered in most human tumors. The retinoblastoma family of proteins plays a key role in regulating the progression of the cell cycle from the G1 to S phases. This is achieved through negative regulation of E2F transcription factors, important positive regulators of cell cycle entry. E2F family members are divided into two groups: activators (E2F1-E2F3a) and repressors (E2F3b-E2F8). E2F4 accounts for a large part of the E2F activity and is a main E2F repressor member in vivo. Perturbations in the balance from quiescence towards proliferation contribute to increased mitotic gene expression levels frequently observed in cancer. We have previously reported that combined Rb1-Rbl1 or Rb1-E2f1 ablation in epidermis produces important alterations in epidermal proliferation and differentiation, leading to tumor development. However, the possible roles of E2F4 in this context are still to be determined. Here, we show the absence of any discernible phenotype in the skin of mice lacking of E2f4. In contrast, the inducible loss of Rb1 in the epidermis of E2F4-null mice produced multiple skin abnormalities including altered differentiation and proliferation, spontaneous wounds, carcinoma in situ development and stem cell perturbations. All these phenotypic alterations are associated with extensive gene expression changes, the induction of c-myc and the Akt activation. Moreover the whole transcriptome analyses in comparison with previous models generated also revealed extensive changes in multiple repressive complexes and in transcription factor activity. These results point to E2F4 as a master regulator in multiple steps of epidermal homeostasis in Rb1 absence.
710			_9625 _aInstituto de Investigación imas12
856			_uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342772/pdf/oncotarget-07-75712.pdf _yAcceso libre
942			_2ddc _cART _n0