title: Distinct gene expression phenotypes of cells lacking Rb and Rb family members.
abstract: The study of tumor suppressor gene function has been aided by the creation of discrete gene alterations in the mouse. One such example can be seen in the study of tumor suppressor gene function in general and the retinoblastoma (Rb) tumor suppressor in particular. Because the phenotype of a cell is a direct reflection of the gene activity within that cell, a comprehensive analysis of changes in gene activity resulting from the loss of Rb function has the potential to greatly enhance our understanding of Rb biology. We have used DNA microarray analysis to identify gene expression profiles in wild-type and Rb-null mouse embryo fibroblasts, as well as cells lacking other Rb family members, as an approach to developing a more complete understanding of Rb function. In so doing, we have identified gene expression phenotypes that characterize the loss of Rb function, that distinguish a Rb-null cell from a wild-type cell as well as a p107/p130-null cell, and that identify gene regulatory pathways unique to these events. Importantly, the Rb gene expression patterns can identify murine tumors that result from Rb loss of function. We suggest that this is an approach to the eventual understanding of gene regulatory pathways that define a phenotypic state, including those events that lead to tumor development.
authors.affiliation: Department of Molecular Genetics and Microbiology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Esther P
authors.initials: EP
authors.lastname: Black
authors.forename: Erich
authors.initials: E
authors.lastname: Huang
authors.forename: Holly
authors.initials: H
authors.lastname: Dressman
authors.forename: Rachel
authors.initials: R
authors.lastname: Rempel
authors.forename: Nina
authors.initials: N
authors.lastname: Laakso
authors.forename: Sylvia L
authors.initials: SL
authors.lastname: Asa
authors.forename: Seiichi
authors.initials: S
authors.lastname: Ishida
authors.forename: Mike
authors.initials: M
authors.lastname: West
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Nevins
mesh_terms: D000818:Animals; D017353:Gene Deletion; D005786:Gene Expression Regulation; D016161:Genes, Retinoblastoma; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D016160:Retinoblastoma Protein / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
chemical_list: D016160:Retinoblastoma Protein