AC61 Vector vs. pRb
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE12637 | GEO | 2009/01/01
SECONDARY ACCESSION(S): PRJNA112817
REPOSITORIES: GEO
Similar Datasets
Project description:This experiment is to identify genes that are regulated by pRb in AC61 cells. AC61 cells were derived from a C-cell adenocarcinoma developed in an Rb+/-N-ras-/- mouse. Experiment Overall Design: AC61 cells were infected with retrovirus derived from pLXSB or pLSXB-Rb and selected with balsticidin for 36 hours. At 72 hour after infection, cells were quickly frozen.
2009-01-14 | E-GEOD-12637 | biostudies-arrayexpress
Project description:RBP2 is downstream of pRB pathway We used gene expression profiling experiments to investigate if gene expression changes in cells with RBP2 knockdown significantly overlap with gene expression changes in cells overexpressing pRB, consistent with the data that knockdown of RBP2 phenocopies reintroduction of pRB in SAOS-2 (RB-/-) cells Keywords: epistatic experiment
2008-08-29 | GSE9690 | GEO
Project description:The specific deletion of Rb gene in epidermis leads to altered proliferation and differentiation, but not to the development of spontaneous tumors. Our previous data have demonstrated the existence of a functional compensation of Rb loss by Rbl1 (p107) in as the phenotypic differences with respect to controls are intensified. However, the possible evolution of this aggravated phenotype, in particular in relationship with tumorigenesis, has not been evaluated due to the premature death of the double deficient mice. We have now investigated whether p107 can also act as a tumor suppressor in pRb-deficient epidermis using different experimental approaches. We found spontaneous tumor development in doubly-deficient skin grafts. Moreover, Rb-deficient keratinocytes are susceptible to Ha-ras-induced transformation, and this susceptibility is enhanced by p107 loss. Further functional analyses, including microarray gene expression profiling, indicated that the loss of p107, in the absence of pRb, produces the reduction of p53-dependent pro-apoptotic signals. Overall, our data demonstrate that p107 behaves as a tumor suppressor in epidermis in the absence of pRb and suggest novel tumor-suppressive roles for p107 in the context of functional p53 and activated Ras Keywords: epidermis, tumorigenesis, pRb, p107, Ras, p53, apoptosis
2007-11-13 | GSE9567 | GEO
Project description:RBP2 is downstream of pRB pathway; We used gene expression profiling experiments to investigate if gene expression changes in cells with RBP2 knockdown significantly overlap with gene expression changes in cells overexpressing pRB, consistent with the data that knockdown of RBP2 phenocopies reintroduction of pRB in SAOS-2 (RB-/-) cells Experiment Overall Design: Knockdown of RBP2 by siRNA to RBP2 (RBP2siRNA) in SAOS-2 (RB-/-) cells in comparison to overexpression of pRB in the SOAS-2 (RB-/-) cells and scrambled version of the RBP2 siRNA (RBP2scsiRNA)
2008-10-25 | E-GEOD-9690 | biostudies-arrayexpress
Project description:The specific deletion of Rb gene in epidermis leads to altered proliferation and differentiation, but not to the development of spontaneous tumors. Our previous data have demonstrated the existence of a functional compensation of Rb loss by Rbl1 (p107) in as the phenotypic differences with respect to controls are intensified. However, the possible evolution of this aggravated phenotype, in particular in relationship with tumorigenesis, has not been evaluated due to the premature death of the double deficient mice. We have now investigated whether p107 can also act as a tumor suppressor in pRb-deficient epidermis using different experimental approaches. We found spontaneous tumor development in doubly-deficient skin grafts. Moreover, Rb-deficient keratinocytes are susceptible to Ha-ras-induced transformation, and this susceptibility is enhanced by p107 loss. Further functional analyses, including microarray gene expression profiling, indicated that the loss of p107, in the absence of pRb, produces the reduction of p53-dependent pro-apoptotic signals. Overall, our data demonstrate that p107 behaves as a tumor suppressor in epidermis in the absence of pRb and suggest novel tumor-suppressive roles for p107 in the context of functional p53 and activated Ras Experiment Overall Design: Pools from RNA whole skin extracts from 3 animals of same genotype were done and analyzed, per duplicate, in mouse microarrays. Comparison was performed between the 4 different genotypes.
2008-06-16 | E-GEOD-9567 | biostudies-arrayexpress
Project description:Homozygous mutation of the murine retinoblastoma tumor suppressor gene, Rb, results in embryonic lethality between E13.5 and E15.5 with defects in cellular proliferation, differentiation and apoptosis. Many of these defects are suppressed by mutation of an activating E2F, E2f1 or E2f3, indicating that they are key downstream targets of the retinoblastoma protein, pRB. In this study, we assess how E2F4 contributes to the developmental consequences of pRb-loss. In stark contrast to the activating E2Fs, the homozygous mutation of E2f4 shortened the lifespan of Rb-/- embryos. This resulted from an exacerbation of the placental defect of the Rb-/- mice indicating that E2F4 and pRB cooperate in the development of this tissue. Further analyses indicated that this defect reflects an increase in trophectoderm-like cells. Under conditions where the placenta was wild-type but the embryo mutant for E2f4 and pRb embryos survived to birth and exhibited all of the defects that were observed in the E2f4 and Rb single mutant embryos. Thus, while pRB and E2F4 cooperate in placental development, they play largely non-overlapping roles the development of many embryonic tissues. Keywords: genetically modified tissue comparison
2009-06-08 | GSE13753 | GEO
Project description: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. Experiment Overall Design: Total RNA from pooled cells from each genotype were analyzed, per duplicate (pRb-/-;p107-/-, or pRb-/-;p130-/-) or triplicate (wild type, or pRb-/-), in mouse microarrays. Comparison was performed between the 4 different genotypes.
2008-06-16 | E-GEOD-9562 | biostudies-arrayexpress
Project description:Homozygous mutation of the murine retinoblastoma tumor suppressor gene, Rb, results in embryonic lethality between E13.5 and E15.5 with defects in cellular proliferation, differentiation and apoptosis. Many of these defects are suppressed by mutation of an activating E2F, E2f1 or E2f3, indicating that they are key downstream targets of the retinoblastoma protein, pRB. In this study, we assess how E2F4 contributes to the developmental consequences of pRb-loss. In stark contrast to the activating E2Fs, the homozygous mutation of E2f4 shortened the lifespan of Rb-/- embryos. This resulted from an exacerbation of the placental defect of the Rb-/- mice indicating that E2F4 and pRB cooperate in the development of this tissue. Further analyses indicated that this defect reflects an increase in trophectoderm-like cells. Under conditions where the placenta was wild-type but the embryo mutant for E2f4 and pRb embryos survived to birth and exhibited all of the defects that were observed in the E2f4 and Rb single mutant embryos. Thus, while pRB and E2F4 cooperate in placental development, they play largely non-overlapping roles the development of many embryonic tissues. Experiment Overall Design: In one experiment, embryonic Day 13.5 placentas from wild-type and Rb -/- knock-out mice were compared. In the second experiment, embronic day 11.5 placentas from wild-type and Rb -/-;E2f4 -/- double knock-out mice were compared.
2009-06-24 | E-GEOD-13753 | biostudies-arrayexpress
Project description:The retinoblastoma tumor suppressor gene (RB) product has been implicated in epigenetic control of gene expression owing to its ability to physically bind to many of chromatin modifiers. However, the biological and clinical significance of this activity was not well elucidated. To address this, we performed genetic and epigenetic analyses in an Rb-deficient mouse thyroid C cell tumor model. Here we report that the genetic interaction of Rb and ATM regulates DNMT1 protein stability, and hence controls the DNA methylation status in the promoter of at least Ink4a, Shc2, FoxO6 and Noggin genes. Further, we demonstrate that inactivation of pRB promotes the Tip60 (acetyltransferase)-dependent ATM activation, allows activated ATM to physically bind to DNMT1 forming a complex with Tip60 and UHRF1 (E3 ligase), and consequently accelerates DNMT1 ubiquitination driven by Tip60-dependent acetylation. Our results indicate that inactivation of pRB pathway in coordination with aberration in DNA damage response leads to abnormal DNA methylation pattern by affecting the stability of DNMT1. 163; Rb-/-;ATM-/- MEFs, D4; DNMT1 knockdown from 163 cells and analysed at day 4, WT8S; 163 cells reconstituted with ATM expression vector
2013-05-31 | E-GEOD-47501 | biostudies-arrayexpress
Project description:The retinoblastoma tumor suppressor gene (RB) product has been implicated in epigenetic control of gene expression owing to its ability to physically bind to many of chromatin modifiers. However, the biological and clinical significance of this activity was not well elucidated. To address this, we performed genetic and epigenetic analyses in an Rb-deficient mouse thyroid C cell tumor model. Here we report that the genetic interaction of Rb and ATM regulates DNMT1 protein stability, and hence controls the DNA methylation status in the promoter of at least Ink4a, Shc2, FoxO6 and Noggin genes. Further, we demonstrate that inactivation of pRB promotes the Tip60 (acetyltransferase)-dependent ATM activation, allows activated ATM to physically bind to DNMT1 forming a complex with Tip60 and UHRF1 (E3 ligase), and consequently accelerates DNMT1 ubiquitination driven by Tip60-dependent acetylation. Our results indicate that inactivation of pRB pathway in coordination with aberration in DNA damage response leads to abnormal DNA methylation pattern by affecting the stability of DNMT1.
2013-05-31 | GSE47501 | GEO