Gene expression data from FGFR3 induced mouse bladder tumors
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ABSTRACT:
PROVIDER: PRJNA637591 | ENA |
REPOSITORIES: ENA
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Project description:Somatic mutations of the fibroblast growth factor receptor 3 (FGFR3) are one of the most frequent genetic alterations in bladder carcinomas. We report here that human-FGFR3-S249C expression in urothelial cells of transgenic mice induces low-grade papillary tumors presenting genomic instability and resembling human pTa urothelial tumors at the transcriptomic level. Mutated-FGFR3 expression levels impacted the incidence of tumor formation and could account for the tissue specificity of human mutated FGFR3-driven tumors restricted to epithelia presenting high normal expression levels of FGFR3.
2021-12-31 | GSE151888 | GEO
Project description:Aberrant activation of FGFR3 via overexpression or mutation is a frequent feature of bladder cancer; however, its molecular and cellular consequences and functional relevance to carcinogenesis are not well understood. In this study with a bladder carcinoma cell line expressing inducible FGFR3 shRNAs, we sought to identiy transcriptional targets of FGFR3 and investigate their contribution to bladder cancer development. Bladder cancer cell line RT112 was transduced with a doxycycline-inducible control EGFP shRNA or three independent FGFR3 shRNAs, designated FGFR3 shRNA 2-4, FGFR3 shRNA 4-1 and FGFR3 shRNA 6-16. These four cell lines were treated with or without doxycycline for 48 hr to deplete FGFR3 protein prior to the isolation of mRNA for microarray analysis. Genes that were differentially expressed after doxycycline induction in all three FGFR3-depleted cell lines but not in the control cell line were considered potential FGFR3-regulated genes. Each treatment group was run in triplcates, and there are 24 samples.
2012-11-07 | E-GEOD-41035 | biostudies-arrayexpress
Project description:Aberrant activation of FGFR3 via overexpression or mutation is a frequent feature of bladder cancer; however, its molecular and cellular consequences and functional relevance to carcinogenesis are not well understood. In this study with a bladder carcinoma cell line expressing inducible FGFR3 shRNAs, we sought to identiy transcriptional targets of FGFR3 and investigate their contribution to bladder cancer development.
2012-11-07 | GSE41035 | GEO
Project description:The NFM-NM-:B transcription factor is constitutively active in a number of hematologic and solid tumors, and many signaling pathways implicated in cancer are likely connected to NFM-NM-:B activation. A critical mediator of NFM-NM-:B activity is TGFM-NM-2-activated kinase 1 (TAK1). Here, we identify TAK1 as a novel interacting protein and direct target of fibroblast growth factor receptor 3 (FGFR3) tyrosine kinase activity. We further demonstrate that activating mutations in FGFR3 associated with both multiple myeloma and bladder cancer can modulate expression of genes which regulate NFM-NM-:B signaling, and promote both NFM-NM-:B transcriptional activity and cell adhesion in a manner dependent on TAK1 expression in both cancer cell types. Our findings suggest TAK1 as a potential therapeutic target for FGFR3-associated cancers, and other malignancies in which TAK1 contributes to constitutive NFM-NM-:B activation. A total of 12 samples of MGHU3 (Y375C) mutant FGFR3 bladder cancer cells (a kind gift from Dr. Margaret Knowles (University of Leeds, Leeds, UK)) were used for array-based gene expression analysis. 3 replicates of each condition: Control siRNA, Control siRNA + PD173074, TAK1 siRNA, and TAK1 siRNA + PD173074.
2013-11-19 | E-GEOD-52452 | biostudies-arrayexpress
Project description:To better understand the molecular mechanisms underlying altered-FGFR3 oncogenic activity in bladder carcinomas, we made use of RT112 cell lines, which were derived from a human bladder tumor and endogenously expressed the FGFR3-TACC3 fusion protein, the growth and transformation of these cell lines being dependent on activated-FGFR3 activity. We conducted a gene expression analysis using Affymetrix DNA arrays in this cell line treated or not with FGFR3 siRNAs.
2018-02-16 | GSE84732 | GEO
Project description:To better understand the molecular mechanisms underlying altered-FGFR3 oncogenic activity in bladder carcinomas, we made use of MGH-U3 cell lines, which were derived from a human bladder tumor and endogenously expressed a mutated activated form of FGFR3 (FGFR3-Y375C), the growth and transformation of these cell lines being dependent on activated-FGFR3 activity. We conducted a gene expression analysis using Affymetrix DNA arrays in this cell line treated or not with FGFR3 siRNAs.
2018-02-16 | GSE84731 | GEO
Project description:Bladder cancer prognosis is closely linked to the underlying differentiation state of the tumor, ranging from the less aggressive and most differentiated luminal tumors to the more aggressive and least differentiated basal tumors. Sequencing of bladder cancer has revealed that loss-of-function mutations in chromatin regulators and mutations that activate receptor tyrosine kinase (RTK) signaling frequently occur in bladder cancer. However, little is known as to whether and how these two types of mutations functionally interact or cooperate to regulate tumor growth and differentiation state. Here, we focus on loss of the histone demethylase UTX (also known as KDM6A) and activation of the RTK FGFR3, two events that commonly co-occur in muscle invasive bladder tumors. We show that UTX loss and FGFR3 activation cooperate to disrupt the balance of luminal and basal gene expression in bladder cells. UTX localized to enhancers surrounding many genes that are important for luminal cell fate, and supported the transcription of these genes in a catalytic-independent manner. In contrast to UTX, FGFR3 activation was associated with lower expression of luminal genes in tumors and FGFR inhibition increased transcription of these same genes in cell culture models. This suggests an antagonistic relationship between UTX and FGFR3. In support of this model, UTX loss-of-function potentiated FGFR3-dependent transcriptional effects and the presence of UTX blocked an FGFR3-mediated increase in the colony formation of bladder cells. Taken together, our study reveals how mutations in UTX and FGFR3 converge to disrupt bladder differentiation programs that could serve as a therapeutic target.
2020-09-15 | GSE157089 | GEO
Project description:Bladder cancer prognosis is closely linked to the underlying differentiation state of the tumor, ranging from the less aggressive and most differentiated luminal tumors to the more aggressive and least differentiated basal tumors. Sequencing of bladder cancer has revealed that loss-of-function mutations in chromatin regulators and mutations that activate receptor tyrosine kinase (RTK) signaling frequently occur in bladder cancer. However, little is known as to whether and how these two types of mutations functionally interact or cooperate to regulate tumor growth and differentiation state. Here, we focus on loss of the histone demethylase UTX (also known as KDM6A) and activation of the RTK FGFR3, two events that commonly co-occur in muscle invasive bladder tumors. We show that UTX loss and FGFR3 activation cooperate to disrupt the balance of luminal and basal gene expression in bladder cells. UTX localized to enhancers surrounding many genes that are important for luminal cell fate, and supported the transcription of these genes in a catalytic-independent manner. In contrast to UTX, FGFR3 activation was associated with lower expression of luminal genes in tumors and FGFR inhibition increased transcription of these same genes in cell culture models. This suggests an antagonistic relationship between UTX and FGFR3. In support of this model, UTX loss-of-function potentiated FGFR3-dependent transcriptional effects and the presence of UTX blocked an FGFR3-mediated increase in the colony formation of bladder cells. Taken together, our study reveals how mutations in UTX and FGFR3 converge to disrupt bladder differentiation programs that could serve as a therapeutic target.
2020-09-15 | GSE157090 | GEO
Project description:To better understand the molecular mechanisms underlying altered-FGFR3 oncogenic activity in bladder carcinomas, we made use of UMUC-14 cell lines, which endogenously expressed a mutated activated form of FGFR3 (FGFR3-S249C), the growth and transformation of these cell lines being dependent on activated-FGFR3 activity. We conducted a gene expression analysis using Affymetrix DNA arrays in this cell line treated or not with FGFR3 siRNAs.
2020-12-31 | GSE125547 | GEO
Project description:Activating mutations of FGFR3 are found in a high proportion of bladder tumours. The molecular consequences of FGFR3 mutation in urothelial cells and the mechanisms by which mutant FGFR3 may drive bladder tumourigenesis are largely unknown. We used expression arrays to identify downstream targets of mutant FGFR3 signalling in normal urothelial cells. TERT-immortalized normal urothelial cells stably transduced to express the most common FGFR3 mutation (S249C) were compared with control cells transduced with the empty vector (pFB).
2014-09-12 | E-GEOD-61352 | biostudies-arrayexpress