Gene expression profiling of noninvasive primary urothelial tumours using microarrays

Aaboe, Mads; Marcussen, Niels; Jensen, Klaus M.E.; Thykjær, Thomas; Dyrskjøt, Lars; Ørntoft, Torben F.

doi:10.1038/sj.bjc.6602813

Cited by 55 publications

(50 citation statements)

References 31 publications

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“…Affymetrix microarray analyses on HeLa cells depleted of Hsp70-1 or Hsp70-2 as well as on bladder and colon biopsies were published previously (10,(26)(27)(28)(29). Data were normalized either using the guanine cytosine content adjusted-robust multiarray (GC-RMA) procedure (HG-U133A; ref.…”

Section: Methodsmentioning

confidence: 99%

Lens Epithelium-Derived Growth Factor Is an Hsp70-2 Regulated Guardian of Lysosomal Stability in Human Cancer

et al. 2007

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Heat shock protein 70-2 (Hsp70-2) is a chaperone protein essential for the growth of spermatocytes and cancer cells. Here, we show that Hsp70-2 depletion triggers lysosomal membrane permeabilization and cathepsin-dependent cell death and identify lens epithelium-derived growth factor (LEDGF) as an Hsp70-2-regulated guardian of lysosomal stability in human cancer. Knockdown of LEDGF in cancer cells induces destabilization of lysosomal membranes followed by caspase-independent and Bcl-2-resistant cell death. Accordingly, ectopic LEDGF stabilizes lysosomes and protects cancer cells against cytotoxicity induced by anticancer agents that trigger the lysosomal cell death pathway. Remarkably, ectopic LEDGF also increases the tumorigenic potential of human cancer cells in immunodeficient mice, and LEDGF expression is increased in human breast and bladder carcinomas correlating with that of Hsp70-2 in invasive bladder cancer. Taken together, these data reveal LEDGF as an oncogenic protein that controls a caspase-independent lysosomal cell death pathway. [Cancer Res 2007;67(6):2559-67]

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Section: Methodsmentioning

confidence: 99%

Lens Epithelium-Derived Growth Factor Is an Hsp70-2 Regulated Guardian of Lysosomal Stability in Human Cancer

et al. 2007

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“…miR-129 targets were identified from the TargetScan prediction algorithm. In addition, we used previously published gene expression data sets to investigate changes in transcript levels of miRNA targets between the groups: normal versus cancer, Ta versus T2, no carcinoma in situ (CIS) versus CIS, and no progression versus progression (22)(23)(24). Genes were defined as being up-regulated or down-regulated when regulated >2-fold between the groups investigated and when the difference was statistically significant (P < 0.01, Student's t test).…”

Section: Methodsmentioning

confidence: 99%

Genomic Profiling of MicroRNAs in Bladder Cancer: miR-129 Is Associated with Poor Outcome and Promotes Cell Death In vitro

Dyrskjøt¹,

Ostenfeld²,

et al. 2009

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microRNAs (miRNA) are involved in cancer development and progression, acting as tumor suppressors or oncogenes. Here, we profiled the expression of 290 unique human miRNAs in 11 normal and 106 bladder tumor samples using spotted locked nucleic acid-based oligonucleotide microarrays. We identified several differentially expressed miRNAs between normal urothelium and cancer and between the different disease stages. miR-145 was found to be the most down-regulated in cancer compared with normal, and miR-21 was the most upregulated in cancer. Furthermore, we identified miRNAs that significantly correlated to the presence of concomitant carcinoma in situ. We identified several miRNAs with prognostic potential for predicting disease progression (e.g., miR-129, miR-133b, and miR-518c*). We localized the expression of miR-145, miR-21, and miR-129 to urothelium by in situ hybridization. We then focused on miR-129 that exerted significant growth inhibition and induced cell death upon transfection with a miR-129 precursor in bladder carcinoma cell lines T24 and SW780 cells. Microarray analysis of T24 cells after transfection showed significant miR-129 target downregulation (P = 0.0002) and pathway analysis indicated that targets were involved in cell death processes. By analyzing gene expression data from clinical tumor samples, we identified significant expression changes of target mRNA molecules related to the miRNA expression. Using luciferase assays, we documented a direct link between miR-129 and the two putative targets GALNT1 and SOX4. The findings reported here indicate that several miRNAs are differentially regulated in bladder cancer and may form a basis for clinical development of new biomarkers for bladder cancer. [Cancer Res 2009;69(11):4851-60]

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“…We analysed the impact of FGFR3 mutations and chromosomal changes on the classification results. Moreover, we used genome-wide gene expression results obtained with Affymetrix 1 GeneChip 1 U133A microarrays 8,22 to identify candidate genes differentially expressed in regions with frequent copy number alterations / allelic imbalance identified in the present study. This dataset included normal controls and microdissected CIS-samples from cystectomy specimens.…”

Section: Gene Expression Analysesmentioning

confidence: 99%

Consistent genomic alterations in carcinoma in situ of the urinary bladder confirm the presence of two major pathways in bladder cancer development

Zieger

Marcussen

Borre

et al. 2009

Intl Journal of Cancer

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Bladder cancer develops through different pathways, provisionally entitled ''papillary'' and ''invasive.'' Carcinoma in situ (CIS) is thought to be the precursor of invasive bladder cancer. However, little is known about chromosomal alterations of these clinically important lesions, and the relationship between chromosomal alterations and the different pathways. We laser-microdissected 12 CIS and 4 dysplasia samples concomitant to invasive bladder cancer. We determined genome-wide chromosome copy number changes and loss of heterozygosity (LOH) using Mapping 10K SNP microarrays. We further examined 48 high-risk nonmuscle-invasive bladder cancers using SNP microarrays to reveal characteristic changes correlated with the CIS-phenotype. DNA copy-number changes were further validated using QPCR in 77 independent tumor samples. CIS was found to be chromosomal unstable in 8 of 12 cases. Characteristic chromosomal changes were copy number gains of chromosomes 5p, 6p22.3, 10p15.1 and losses/LOH of chromosome 5q and 13q13-q14. Tumor samples with these alterations were significantly associated with CIS. Using FGFR3 mutations as markers of the opposing papillary phenotype, we found 5p gains and FGFR3 mutations mutually exclusive. No FGFR3 mutations were found in 23 CIS and dysplasia samples. Based on this, we classified high-risk non-muscle-invasive bladder tumors according to FGFR3 mutations and chromosomal changes into papillary and CIS-type tumors with high correlation to CIS status (p 5 0.001). Furthermore, we found significant correlation to the results of molecular classifiers based on gene-expression. We concluded that chromosomal changes may be used to characterize different pathways in bladder cancer development. ' 2009 UICC

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Gene expression profiling of noninvasive primary urothelial tumours using microarrays

Cited by 55 publications

References 31 publications

Lens Epithelium-Derived Growth Factor Is an Hsp70-2 Regulated Guardian of Lysosomal Stability in Human Cancer

Lens Epithelium-Derived Growth Factor Is an Hsp70-2 Regulated Guardian of Lysosomal Stability in Human Cancer

Genomic Profiling of MicroRNAs in Bladder Cancer: miR-129 Is Associated with Poor Outcome and Promotes Cell Death In vitro

Consistent genomic alterations in carcinoma in situ of the urinary bladder confirm the presence of two major pathways in bladder cancer development

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