Sustaining Cyclin D1 Expression Renders Kidney Cancer Cells HIF2-Independent
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ABSTRACT:
PROVIDER: PRJNA1160283 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR30648736_1.fastq.gz | Fastqsanger.gz | |||
| SRR30648736_2.fastq.gz | Fastqsanger.gz | |||
| SRR30648737_1.fastq.gz | Fastqsanger.gz | |||
| SRR30648737_2.fastq.gz | Fastqsanger.gz |
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Project description:Sustaining Cyclin D1 Expression Renders Kidney Cancer Cells HIF2-Independent
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Project description:Sustaining Cyclin D1 Expression Renders Kidney Cancer Cells HIF2-Independent
| PRJNA1160285 | ENA
Project description:Sustaining Cyclin D1 Expression Renders Kidney Cancer Cells HIF2-Independent
| PRJNA1160286 | ENA
Project description:Inactivation of theVHLtumor suppressor gene stabilizes HIF2a, which drives clear cell renal carcinoma (ccRCC). The HIF2ainhibitor belzutifan is approved for ccRCC treatment, butde novoand acquiredresistance are common. HIF2a, bound to ARNT, transcriptionally activates hundreds of genes. We performed genome-wide CRISPRa screens in HIF2a-dependent ccRCC lines treated with the belzutifan tool compound PT2399 to identify HIF2a-responsive genes that confer belzutifan resistance when not downregulated. Sustaining the expression of the HIF2atarget geneCCND1, encoding Cyclin D1, promoted HIF2a-independence/belzutifan resistance. This activity requires Cdk4/6 activation by Cyclin D1, but is not solely due to inhibitory phosphorylation of the canonical Cyclin D1 target, pRB. Indeed, ccRCC lines lacking all three pRB family members remained at least partially HIF2a-dependent. In this context. However, kinase-defective Cyclin D1 variants at least partially overrode belzutifan’s antiproliferative effects, suggesting that ccRCC promotion by Cyclin D1 requires the phosphorylation of pRB paralogs and one or more kinase-independent Cyclin D1 activities.
2025-03-20 | GSE277045 | GEO
Project description:Inactivation of theVHLtumor suppressor gene stabilizes HIF2a, which drives clear cell renal carcinoma (ccRCC). The HIF2ainhibitor belzutifan is approved for ccRCC treatment, butde novoand acquiredresistance are common. HIF2a, bound to ARNT, transcriptionally activates hundreds of genes. We performed genome-wide CRISPRa screens in HIF2a-dependent ccRCC lines treated with the belzutifan tool compound PT2399 to identify HIF2a-responsive genes that confer belzutifan resistance when not downregulated. Sustaining the expression of the HIF2atarget geneCCND1, encoding Cyclin D1, promoted HIF2a-independence/belzutifan resistance. This activity requires Cdk4/6 activation by Cyclin D1, but is not solely due to inhibitory phosphorylation of the canonical Cyclin D1 target, pRB. Indeed, ccRCC lines lacking all three pRB family members remained at least partially HIF2a-dependent. In this context. However, kinase-defective Cyclin D1 variants at least partially overrode belzutifan’s antiproliferative effects, suggesting that ccRCC promotion by Cyclin D1 requires the phosphorylation of pRB paralogs and one or more kinase-independent Cyclin D1 activities.
2025-03-20 | GSE277044 | GEO
Project description:Inactivation of theVHLtumor suppressor gene stabilizes HIF2a, which drives clear cell renal carcinoma (ccRCC). The HIF2ainhibitor belzutifan is approved for ccRCC treatment, butde novoand acquiredresistance are common. HIF2a, bound to ARNT, transcriptionally activates hundreds of genes. We performed genome-wide CRISPRa screens in HIF2a-dependent ccRCC lines treated with the belzutifan tool compound PT2399 to identify HIF2a-responsive genes that confer belzutifan resistance when not downregulated. Sustaining the expression of the HIF2atarget geneCCND1, encoding Cyclin D1, promoted HIF2a-independence/belzutifan resistance. This activity requires Cdk4/6 activation by Cyclin D1, but is not solely due to inhibitory phosphorylation of the canonical Cyclin D1 target, pRB. Indeed, ccRCC lines lacking all three pRB family members remained at least partially HIF2a-dependent. In this context. However, kinase-defective Cyclin D1 variants at least partially overrode belzutifan’s antiproliferative effects, suggesting that ccRCC promotion by Cyclin D1 requires the phosphorylation of pRB paralogs and one or more kinase-independent Cyclin D1 activities.
2025-03-20 | GSE277043 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-03-20 | GSE277046 | GEO
Project description:Analysis of mammary glands from tet-inducible(rtTA) transgenic mice expressing cyclin D1 using Affymetrix Mouse Gene 1.0 ST GeneChip arrays. MMTV-rtTA transgenic mice (MMTV-Mouse Mammary Tumor Virus promoter) were cross-mated to cyclin D1 transgenic mice under control of tet operon. 8-week-old tetracycline-inducible cyclin D1/rtTA bi-transgenic pregnant female mice (12 days postcoitus) were treated with doxycycline through drinking water supplementation at a final concentration of 2 mg/ml. Control mice were rtTA transgenics alone and treated in the same manner. After 7 days of doxycycline treatment, the mice were sacrificed and mammary glands taken for RNA isolation. Results provide insight into the in vivo gene expression pattern regulated by cyclin D1 through acute induction. Analysis of mammary glands from MMTV-cyclin D1/WT and MMTV-cyclin D1/KE using Affymetrix Mouse 430A v2.0 GeneChip arrays. Cyclin D1 point mutant, cyclin D1/KE K112E (K112E) contains a lysine to glutamine substitution at amino acid position 112. cyclin D1. The cyclin D1/KE mutant fails to induce cyclin D1-dependent kinase activity. Female MFD1, MFD1-KE, and WT mice were monitored twice weekly, up to 760 days, for the development of palpable tumors. Those developing palpable tumors were sacrificed within a week of tumor detection. Tumors were dissected and portions snap frozen for RNA isolation. Results provide insight into the in vivo gene expression pattern regulated by cyclin D1 that is kinase independent.
2013-12-31 | GSE43216 | GEO
Project description:Analysis of mammary glands from tet-inducible(rtTA) transgenic mice expressing cyclin D1 using Affymetrix Mouse Gene 1.0 ST GeneChip arrays. MMTV-rtTA transgenic mice (MMTV-Mouse Mammary Tumor Virus promoter) were cross-mated to cyclin D1 transgenic mice under control of tet operon. 8-week-old tetracycline-inducible cyclin D1/rtTA bi-transgenic pregnant female mice (12 days postcoitus) were treated with doxycycline through drinking water supplementation at a final concentration of 2 mg/ml. Control mice were rtTA transgenics alone and treated in the same manner. After 7 days of doxycycline treatment, the mice were sacrificed and mammary glands taken for RNA isolation. Results provide insight into the in vivo gene expression pattern regulated by cyclin D1 through acute induction. Analysis of mammary glands from MMTV-cyclin D1/WT and MMTV-cyclin D1/KE using Affymetrix Mouse 430A v2.0 GeneChip arrays. Cyclin D1 point mutant, cyclin D1/KE K112E (K112E) contains a lysine to glutamine substitution at amino acid position 112. cyclin D1. The cyclin D1/KE mutant fails to induce cyclin D1-dependent kinase activity. Female MFD1, MFD1-KE, and WT mice were monitored twice weekly, up to 760 days, for the development of palpable tumors. Those developing palpable tumors were sacrificed within a week of tumor detection. Tumors were dissected and portions snap frozen for RNA isolation. Results provide insight into the in vivo gene expression pattern regulated by cyclin D1 that is kinase independent. Two separate control mice were positive for MMTV-rtTA transgene compared to 3 separate cyclin D1/rtTA bitransgenic female mice and 3 separate cyclin D1 KE mutant/rtTA bitransgenic female mice (Mouse Gene 1.0 ST arrays). Three separate control WT FvBmice were compared to three MMTV-cyclin D1/WT and 3 MMTV-cyclin D1/KE mice (Mouse 430A v2.0 arrays).
2013-12-31 | E-GEOD-43216 | biostudies-arrayexpress
Project description:Mantle cell lymphoma (MCL) is an aggressive B-cell neoplasm characterized by the t(11;14)(q13;q32) translocation leading to cyclin D1 overexpression. Cyclin D1 is a major cell cycle regulator and also has a role in transcription, but the effect of the latter in tumorigenesis remains largely unknown. Here, we investigated the transcriptional role of cyclin D1 in MCL and its impact on the pathogenesis of this neoplasm. Integrating genome-wide expression analysis of cyclin D1-silenced and overexpressing cells with cyclin D1 chromatin binding profiles, we identified a cyclin D1-activated transcriptional program in MCL cells. We used microarrays to analyze the genome-wide expression modulation in cyclin D1 overexpression models established in the cyclin D1-negative lymphoblastoid cell line JVM13.
2021-06-30 | GSE144095 | GEO