Gene expression profiling of murine tumors derived from Renca control knockout vs Pbrm1 knockout tumor clones
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE145919 | GEO | 2020/02/26
REPOSITORIES: GEO
Similar Datasets
Project description:Gene expression profiling of murine tumors derived from Renca control knockout vs Pbrm1 knockout tumor clones
| PRJNA608734 | ENA
Project description:Tumors can occur in many sites in the body, but how tissues at different anatomical sites affect tumor microenvironments and their subsequent response to therapy is not known. Here we show that different tissues can cause the same tumor to develop fundamentally different microenvironments resulting in dramatic changes in responses to immunotherapy. Whereas established subcutaneous tumors could be eradicated in the majority of mice using a combination of three agonist antibodies, tumors in visceral organs responded much less. Orthotopic kidney tumors had a microenvironment with a higher frequency of alternatively-activated macrophages and their associated molecules. Neutralizing the CCL2 chemokine or IL-13 cytokine, important in macrophage biology led to a greatly improved therapeutic effect. Importantly, a significantly reduced therapeutic response of subcutaneous tumors was observed when visceral tumors were simultaneously present in the same mice. In this study we sought to compare gene expression of mouse renal cell carcinoma cells growing in the kidney to cells growing subcutaneously. Renca is a renal cell carcinoma cell line (Murphy and Hrushesky, 1973). To produce subcutaneous tumors, mice received 2 x 10^5 Renca. Orthotopic tumors were established by first surgically isolating the organ and then injecting 2 x 10^5 Renca cells intrakidney (IK) into the outer cortex of the kidney in 20 ul of PBS. Tumors were removed from mice 12 days after implantation, when approximately 20-30 mm2. Tumors were snap frozen on liquid nitrogen prior to processing for total RNA followed by analysis on Mouse Gene 1.0 chips. Kidney Renca tumors were excised from 3 BALB/c mice and subcutaneous Renca tumors were excised from another 3 BALB/c mice. cDNA was prepared and hybridized to Mouse Gene 1.0 ST chips.
2012-09-08 | E-GEOD-40679 | biostudies-arrayexpress
Project description:PBRM1 was found to be mutated in a high percentage of clear cell RCCs. We performed knockdown of PBRM1 via siRNA and compared with scrambled control in three different RCC cell lines. PBRM1 siRNA and mock treated cell lines were normalized together with 'hypoxic' clear cell renal tumors and normal renal tissue samples from GSE17818.
2011-01-20 | E-GEOD-22316 | biostudies-arrayexpress
Project description:Renca, a murine renal cell carcinoma, and B16F10, a murine melanoma, were transcriptionally profiled in a study designed to accompany an in vivo CRISPR screen to identify novel immunotherapy dependencies.
2020-11-25 | GSE162105 | GEO
Project description:Tumors can occur in many sites in the body, but how tissues at different anatomical sites affect tumor microenvironments and their subsequent response to therapy is not known. Here we show that different tissues can cause the same tumor to develop fundamentally different microenvironments resulting in dramatic changes in responses to immunotherapy. Whereas established subcutaneous tumors could be eradicated in the majority of mice using a combination of three agonist antibodies, tumors in visceral organs responded much less. Orthotopic kidney tumors had a microenvironment with a higher frequency of alternatively-activated macrophages and their associated molecules. Neutralizing the CCL2 chemokine or IL-13 cytokine, important in macrophage biology led to a greatly improved therapeutic effect. Importantly, a significantly reduced therapeutic response of subcutaneous tumors was observed when visceral tumors were simultaneously present in the same mice. In this study we sought to compare gene expression of mouse renal cell carcinoma cells growing in the kidney to cells growing subcutaneously. Renca is a renal cell carcinoma cell line (Murphy and Hrushesky, 1973). To produce subcutaneous tumors, mice received 2 x 10^5 Renca. Orthotopic tumors were established by first surgically isolating the organ and then injecting 2 x 10^5 Renca cells intrakidney (IK) into the outer cortex of the kidney in 20 ul of PBS. Tumors were removed from mice 12 days after implantation, when approximately 20-30 mm2. Tumors were snap frozen on liquid nitrogen prior to processing for total RNA followed by analysis on Mouse Gene 1.0 chips.
2012-09-08 | GSE40679 | GEO
Project description:PBRM1 encodes an accessory subunit of the PBAF subclass of the SWI/SNF chromatin remodeler and the inactivation of PBRM1 is the second most frequent mutational event in kidney cancer. However, the impact of PBRM1 loss on chromatin remodeling, especially pertaining to kidney tumorigenesis, has not been well examined. Here we show that in VHL-deficient renal tumors, PBRM1 deficiency results in aberrant PBAF complexes that localize to de novo genomic loci and activate the pro-tumorigenic NF-?B pathway. PBRM1-deficient PBAF complexes, despite retaining the association between SMARCA4 and ARID2, have loosely tethered BRD7 and redistribute from promoter proximal regions to distal enhancers containing NF-?B motifs. Subsequently, PBRM1-deficient cells display heightened NF-?B activity in multiple models and clinical samples. The ATPase function of SMARCA4 maintains chromatin occupancy of both pre-existing and newly acquired RELA specific to PBRM1 loss, and activates downstream target gene expression. Proteasome inhibitor bortezomib reverses NF-?B activation by reducing RELA occupancy and delays growth of PBRM1-deficient tumors. In conclusion, PBRM1 safeguards the chromatin by repressing aberrant liberation of pro-tumorigenic NF-?B target genes by residual PBRM1-deficient PBAF complexes.
2023-02-13 | GSE152681 | GEO
Project description:PBRM1 encodes an accessory subunit of the PBAF subclass of the SWI/SNF chromatin remodeler and the inactivation of PBRM1 is the second most frequent mutational event in kidney cancer. However, the impact of PBRM1 loss on chromatin remodeling, especially pertaining to kidney tumorigenesis, has not been well examined. Here we show that in VHL-deficient renal tumors, PBRM1 deficiency results in aberrant PBAF complexes that localize to de novo genomic loci and activate the pro-tumorigenic NF-κB pathway. PBRM1-deficient PBAF complexes, despite retaining the association between SMARCA4 and ARID2, have loosely tethered BRD7 and redistribute from promoter proximal regions to distal enhancers containing NF-κB motifs. Subsequently, PBRM1-deficient cells display heightened NF-κB activity in multiple models and clinical samples. The ATPase function of SMARCA4 maintains chromatin occupancy of both pre-existing and newly acquired RELA specific to PBRM1 loss, and activates downstream target gene expression. Proteasome inhibitor bortezomib reverses NF-κB activation by reducing RELA occupancy and delays growth of PBRM1-deficient tumors. In conclusion, PBRM1 safeguards the chromatin by repressing aberrant liberation of pro-tumorigenic NF-κB target genes by residual PBRM1-deficient PBAF complexes.
2023-02-13 | GSE222245 | GEO
Project description:PBRM1 encodes an accessory subunit of the PBAF subclass of the SWI/SNF chromatin remodeler and the inactivation of PBRM1 is the second most frequent mutational event in kidney cancer. However, the impact of PBRM1 loss on chromatin remodeling, especially pertaining to kidney tumorigenesis, has not been well examined. Here we show that in VHL-deficient renal tumors, PBRM1 deficiency results in aberrant PBAF complexes that localize to de novo genomic loci and activate the pro-tumorigenic NF-κB pathway. PBRM1-deficient PBAF complexes, despite retaining the association between SMARCA4 and ARID2, have loosely tethered BRD7 and redistribute from promoter proximal regions to distal enhancers containing NF-κB motifs. Subsequently, PBRM1-deficient cells display heightened NF-κB activity in multiple models and clinical samples. The ATPase function of SMARCA4 maintains chromatin occupancy of both pre-existing and newly acquired RELA specific to PBRM1 loss, and activates downstream target gene expression. Proteasome inhibitor bortezomib reverses NF-κB activation by reducing RELA occupancy and delays growth of PBRM1-deficient tumors. In conclusion, PBRM1 safeguards the chromatin by repressing aberrant liberation of pro-tumorigenic NF-κB target genes by residual PBRM1-deficient PBAF complexes.
2023-02-13 | GSE222244 | GEO
Project description:PBRM1 is an accessory subunit of the PBAF subclass of the SWI/SNF chromatin remodeler. The inactivation of PBRM1 is the second most frequent mutational event in kidney tumorigenesis. Here we show that in VHL-deficient ccRCC tumors, PBRM1 loss results in an altered PBAF complex that retains the association between SMARCA4 and ARID2 but disengages BRD7 from SMARCA4. The PBRM1-deficient PBAF complexes redistribute from promoter proxy regions to distal enhancer regions. The ATPase function of SMARCA4 enhances the recruitment of nuclear factor RELA to aberrant sites and promotes NF-κB activity. Proteasome inhibitor bortezomib reverses NF-κB activation by reducing RELA binding at regions bound by PBRM1-deficient PBAF and delays PBRM1-deficient tumor growth. In conclusion, PBRM1 safeguards the chromatin by repressing aberrant liberation of pro-tumorigenic NF-κB target genes by residual PBRM1-deficient PBAF complexes.
2023-02-13 | GSE152734 | GEO
Project description:Polybromo-1 (PBRM1), which encodes a specific subunit of the pBAF chromatin remodeling complex, is inactivated in multiple malignancies including 50% of clear cell renal cell carcinoma. At present, a therapeutic strategy that selectively targets PBRM1 defects does not exist. PBRM1 is involved in multiple cellular processes including transcription, replication and DNA repair. Using high-throughput screens and multiple isogenic and non-isogenic models, we found that PBRM1 defects cause synthetic lethality with several clinical PARP inhibitors, both in vitro and in vivo. This effect was enhanced using combinations with either small molecule ATR or BET inhibitors. Mechanistically, PBRM1 defects caused increased replication stress, R-loop formation and genomic instability that was exacerbated by PARP inhibitors. We also found that PARP and ATR inhibitors activate the cGAS-STING innate immunity pathway in PBRM1-deficient but not in PBRM1-proficient cells. These data provide the pre-clinical rationale for assessing PARP inhibitors as a monotherapy or in combination with ATR inhibitors or immune checkpoint inhibitors, in patients with PBRM1-deficient cancers.
2022-02-21 | PXD017826 | Pride