title: Gene profiling approaches help to define the specific functions of retinoblastoma family in epidermis.
abstract: The epidermal-specific ablation of Rb gene leads to increased proliferation, aberrant differentiation, and the disengagement of these processes in vivo and in vitro. These differences in phenotype are more severe with the loss of p107, demonstrating the functional compensation between pRb and p107. As p107 and p130 also exert overlapping functions in epidermis, we have generated Rb(F19/F19)K14cre;Rbl2-/- (pRb-;p130-) mice to analyze possible functional redundancies between pRb and p130. The epidermal phenotype was very similar between pRb- and pRb-;p130- mice, suggesting that pRb and p130 activities are not redundant in epidermis. Importantly, we can correlate the proliferation differences with specific changes in gene expression between pRb-, pRb-;p107- and pRb-;p130- primary keratinocytes using microarray analysis, and explain the phenotypes in the context of altered E2F expression and functionality. Our findings support a model in which the distinct retinoblastoma family members, in conjunction with E2F members, play a central role in regulating epidermal homeostasis through specific or overlapping activities.
authors.affiliation: Molecular Oncology Unit, Biomedicine Division, CIEMAT, Madrid, Spain.
authors.forename: M Fernanda
authors.initials: MF
authors.lastname: Lara
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Escudero
authors.forename: Sergio
authors.initials: S
authors.lastname: Ruiz
authors.forename: Mirentxu
authors.initials: M
authors.lastname: Santos
authors.forename: Marta
authors.initials: M
authors.lastname: Moral
authors.forename: Ana B
authors.initials: AB
authors.lastname: Martínez-Cruz
authors.forename: Carmen
authors.initials: C
authors.lastname: Segrelles
authors.forename: Corina
authors.initials: C
authors.lastname: Lorz
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Paramio
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D050684:E2F Transcription Factors / Q000235:genetics / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D015603:Keratinocytes / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D050717:Retinoblastoma-Like Protein p130 / Q000235:genetics / Q000378:metabolism*
chemical_list: D050684:E2F Transcription Factors; C493838:Rbl2 protein, mouse; D016160:Retinoblastoma Protein; D050717:Retinoblastoma-Like Protein p130