Gene profiling approaches help to define the specific functions of retinoblastoma family in epidermis.
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.
Lara
M Fernanda
MF
Molecular Oncology Unit, Biomedicine Division, CIEMAT, Madrid, Spain.
García-Escudero
Ramón
R
Ruiz
Sergio
S
Santos
Mirentxu
M
Moral
Marta
M
Martínez-Cruz
Ana B
AB
Segrelles
Carmen
C
Lorz
Corina
C
Paramio
Jesús M
JM
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*
D050684:E2F Transcription Factors; C493838:Rbl2 protein, mouse; D016160:Retinoblastoma Protein; D050717:Retinoblastoma-Like Protein p130