Novel oncogenic function of ATDC in bladder cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4591-4591
Author(s):  
Phillip Lee Palmbos ◽  
Lidong Wang ◽  
Huibin Yang ◽  
Taylor Detzler ◽  
Gina Ney ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Cancer Cell ◽  
Pten Expression ◽  
Cancer Tissue ◽  
Bladder Tumors ◽  
Human Bladder ◽  
Urothelial Carcinomas ◽  
Normal Bladder

4591 Background: Bladder cancer is a common and deadly disease, but the molecular events leading to its initiation and progression are incompletely understood. We recently identified Ataxia-Telangiectasia Group D Associated (ATDC) as a novel oncogene which drives tumor proliferation and invasion in pancreatic carcinoma (Cancer Cell, 2009). In this study, we describe the role of ATDC as an oncogene in bladder cancer. Methods: To further determine the oncogenic role of ATDC, we generated ATDC transgenic (tg) mice in which ATDC expression was driven by a CMV promoter and characterized the resulting tumors. Results: Interestingly, the dominant phenotype in these mice was the development of both non-invasive and invasive urothelial carcinomas (9% and 20% respectively, average age of onset 10-12 months of age). Histologically, these tumors were indistinguishable from human urothelial carcinomas. Gene expression profiling of invasive tumors derived from ATDC tg mice demonstrated a marked overlap with gene signatures of human invasive bladder cancers. ATDC was the 11th most highly up-regulated gene in bladder cancers represented in the Oncomine gene expression database. Analysis of a human bladder cancer tissue microarray (311 samples) by IHC showed elevated expression in 70% (173/252) of muscle-invasive carcinomas, 22% (5/23) of papillary tumors and little or no expression in normal bladder urothelium. ATDC tg mouse bladder tumors demonstrated loss of p53 signaling and down-regulation of PTEN expression, which correlated with ATDC induced methylation of the PTEN promoter by DNMT3A. Furthermore, ATDC knock-down in invasive cancer cell lines resulted in decreased proliferation, invasion and reactivation of p53-mediated signaling and PTEN expression. Conclusions: ATDC is a novel oncogene that is highly expressed in human bladder cancers and is sufficient to drive the development of invasive bladder tumors in tg mice. The mechanism by which ATDC drives bladder cancer formation involves alterations in p53 and PTEN pathways known to be important in bladder tumorigenesis.

ATDC as a novel oncogene in bladder cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 269-269
Author(s):  
Phillip Lee Palmbos ◽  
Lidong Wang ◽  
Huibin Yang ◽  
Taylor Detzler ◽  
Gina Ney ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Cancer Cell ◽  
Pten Expression ◽  
Cancer Tissue ◽  
Bladder Tumors ◽  
Human Bladder ◽  
Urothelial Carcinomas ◽  
Normal Bladder

269 Background: Bladder cancer is a common and deadly disease, but the molecular events leading to its initiation and progression are incompletely understood. We recently identified Ataxia-Telangiectasia Group D Associated (ATDC) as a novel oncogene which drives tumor proliferation and invasion in pancreatic carcinoma (Cancer Cell, 2009). In this study, we describe the role of ATDC as an oncogene in bladder cancer. Methods: To further determine the oncogenic role of ATDC, we generated ATDC transgenic (tg) mice in which ATDC expression was driven by a CMV promoter and characterized the resulting tumors. Results: The dominant phenotype in these mice was the development of both papillary and invasive urothelial carcinomas (9% and 20% respectively, average age of onset 10-12 months of age). Histologically, these tumors were indistinguishable from human urothelial carcinomas. Gene expression profiling of invasive tumors derived from ATDC tg mice demonstrated a marked overlap with gene signatures of human invasive bladder cancers. Analysis of a human bladder cancer tissue microarray (311 samples) showed elevated expression in 70% (173/252) of muscle-invasive carcinomas, whereas normal bladder had no expression. 22% (5/23) of papillary tumors also expressed elevated levels of ATDC. ATDC was the 11th most highly up-regulated gene in bladder cancers represented in the Oncomine gene expression database. ATDC tg mouse bladder tumors demonstrated loss of p53 signaling and down-regulation of PTEN expression, which was determined to be due to ATDC abrogation of p53 function by cytoplasmic sequestration and ATDC-mediated methylation of the PTEN promoter. Furthermore, ATDC knock-down in invasive cancer cell lines resulted in decreased proliferation, invasion and reactivation of p53-mediated signaling and PTEN expression. Conclusions: ATDC is a novel oncogene that is highly expressed in human bladder cancers and is sufficient to drive the development of invasive bladder tumors in tg mice. The mechanism by which ATDC drives bladder cancer formation involves alterations in p53 and PTEN pathways known to be important in bladder tumorigenesis.

Metallothionein isoform gene expression in four human bladder cancer cell lines

1999 ◽  
pp. 607-612 ◽  
Author(s):  
Scott H. Garrett ◽  
Seema Somji ◽  
John H. Todd ◽  
Donald A. Sens ◽  
Donald L. Lamm ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Bladder Cancer Cell ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Human Bladder Cancer Cell

scholarly journals Neurotensin Branched Peptide as a Tumor-Targeting Agent for Human Bladder Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Jlenia Brunetti ◽  
Chiara Falciani ◽  
Barbara Lelli ◽  
Andrea Minervini ◽  
Niccolò Ravenni ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Tumor Targeting ◽  
Cancer Cell Lines ◽  
Personalized Therapy ◽  
Bladder Cancer Cell ◽  
Cancer Tissue ◽  
Human Bladder Cancer ◽  
Human Bladder

Despite recent advances in multimodal therapy, bladder cancer still ranks ninth in worldwide cancer incidence. New molecules which might improve early diagnosis and therapeutic efficiency for tumors of such high epidemiological impact therefore have very high priority. In the present study, the tetrabranched neurotensin peptide NT4 was conjugated with functional units for cancer-cell imaging or therapy and was tested on bladder cancer cell lines and specimens from bladder cancer surgical resections, in order to evaluate its potential for targeted personalized therapy of bladder cancer. Fluorophore-conjugated NT4 distinguished healthy and cancer tissues with good statistical significanceP<0.05. NT4 conjugated to methotrexate or gemcitabine was cytotoxic for human bladder cancer cell lines at micromolar concentrations. Their selectivity for bladder cancer tissue and capacity to carry tracers or drugs make NT4 peptides candidate tumor targeting agents for tracing cancer cells and for personalized therapy of human bladder cancer.

A chemically-modified miR-21 inhibitor (ADM-21) as a novel potential therapy in bladder cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 335-335 ◽  
Author(s):  
Alexandra Drakaki ◽  
Marina Koutsioumpa ◽  
Neil A. O'Brien ◽  
Christina Vorvis ◽  
Dimitrios Iliopoulos ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Gene Signature ◽  
Bladder Tumors ◽  
Human Bladder ◽  
Chemically Modified ◽  
Direct Target

335 Background: MicroRNAs are key regulators of cancer signaling pathways.Targeting their expression has therapeutic potential. MicroRNA-21 (miR-21) acts as an oncogene in several cancers. Here we describe its functional significance in bladder oncogenesis and the therapeutic properties of a novel chemically-modified miR-21 inhibitor (ADM-21). Methods: MiR-21 expression was assessed by RT-PCR in a panel of human bladder cancer tissues and cell lines. Transcriptomic profiling of 28 bladder cancer cell lines performed to identify miR-21-dependent gene signatures. ADM-21 is a chemically-modified (phosphorothioate backbone and locked-nuclei-acid) antisense oligo against miR-21 with high potency and stability.The efficacy of ADM-21 treatment was evaluated in vitro and in vivo. Results: MiR-21 was up-regulated by 5-fold in bladder tumors relatively to normal tissue and by 3-fold in advanced compared to early stage bladder cancers. The 28 cancer cell lines were stratified in 3 groups (high, intermediate, low) according to miR-21 levels. Transcriptomic analysis revealed a 15-gene signature that negatively correlated with miR-21 levels. Protein Phosphatase 2 Regulatory Subunit B Isoform A (PPP2R2A) displayed tumor suppressive properties in bladder cancer. Moreover, PPP2R2A represents a novel miR-21 direct target gene and a negative regulator of the AKT/mTOR pathway. ADM-21 (10uM) treatment suppressed 43.5% the growth and 90% the invasiveness of 5367 bladder cancer cells. Also, intravenous (I.V.) administration of ADM-21 was proven more effective than intraperitoneal (I.P.) administration in mouse xenografts. Specifically, 15mg/kg of ADM-21 (I.V.) every 5 days for 3 cycles reduced 37% and 47% (day 16) the growth rate of tumors originating from injections of 5367 and RT-112 cells, respectively. Conclusions: Integrative analysis of human bladder tumors and cell lines revealed a novel 15-gene signature that correlates with miR-21 levels. PPP2R2A is a miR-21 direct target and regulator of the AKT/mTOR pathway. ADM-21effectively reduces bladder cancer growth in vitro and in vivo. Upon completion of ADM-21 toxicology studies and confirm safety we will design phase I clinical trial for advanced bladder cancer.

Effects of Diethyl Spermine Analogues in Human Bladder Cancer Cell Lines in Culture

1993 ◽  
Vol 150 (4) ◽  
pp. 1293-1297 ◽  
Author(s):  
Barbara K. Chang ◽  
Yayun Liang ◽  
David W. Miller ◽  
Raymond J. Bergeron ◽  
Carl W. Porter ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Bladder Cancer Cell ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Human Bladder Cancer Cell ◽  
Spermine Analogues

Rab23 is overexpressed in human bladder cancer and promotes cancer cell proliferation and invasion

Tumor Biology ◽  
2015 ◽  
Vol 37 (6) ◽  
pp. 8131-8138 ◽  
Author(s):  
Yuanjun Jiang ◽  
Yushuang Han ◽  
Chaonan Sun ◽  
Chuyang Han ◽  
Ning Han ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Proliferation And Invasion

Characterization of FOXF1 as a novel regulator of nodal metastasis in bladder cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 480-480
Author(s):  
Anirban P Mitra ◽  
Andrea Kokorovic ◽  
Tanner Miest ◽  
Vikram M Narayan ◽  
Debasish Sundi ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Differentially Expressed Gene ◽  
Cancer Cell Lines ◽  
Differentially Expressed ◽  
Bladder Cancer Cell ◽  
Primary Tumors ◽  
Orthotopic Xenografts

480 Background: Members of the forkhead transcription factor (FOX) family are important mediators of embryonic development and are known to be altered in a variety of cancers. The functional role of FOXF1 in bladder tumorigenesis and progression has not been clearly characterized thus far. This study investigated the clinical implications of differential FOXF1 expression in bladder cancer, and potential mechanisms by which its alteration can lead to tumor metastasis. Methods: Whole genome expression profiling was performed on paired primary tumors and nodal metastases from a radical cystectomy discovery cohort using Illumina HT12 v3-4 BeadChip arrays to identify FOXF1 as a top differentially expressed gene. Prognostic role of differential FOXF1 expression was validated on two independent cystectomy cohorts. Differential FOXF1 expression was also evaluated in murine orthotopic xenografts. Small interfering RNA was used to knock down FOXF1 in RT112 and UC6 bladder cancer cell lines to develop an in vitro model for assessment of metastatic potential. Next-generation sequencing and hierarchical clustering analysis were used to identify differentially altered genes secondary to FOXF1 knockdown. 186 biologically curated pathways were interrogated with internal validation to elucidate the downstream biologic mechanisms of metastasis. Results: In the discovery cohort, FOXF1 was a top differentially expressed gene with 3.6-fold lower expression in nodal metastases than paired primary tumors (n = 33, p < 0.001). Multivariable analyses in two validation cohorts (total n = 128) indicated that FOXF1 underexpression was associated with worse cancer-specific (p = 0.046) and overall survival (p = 0.006). Murine orthotopic xenografts (n = 13) established from human bladder cancer cell lines (UC3, UC6, UC14) showed FOXF1 underexpression in metastatic deposits compared with primary tumors (p = 0.004). Hierarchical clustering identified 40 differentially expressed genes between FOXF1-knockdown bladder cancer cell lines and their corresponding controls. Biological pathway interrogation showed differential enrichment for genes associated with mitogen-activated protein kinase signaling, focal adhesion and other carcinogenic pathways in FOXF1-knockdown cells compared with controls (normalized enrichment score ≥ 1.3). Conclusions: We identify and characterize FOXF1 as a novel regulatory molecule that potentially drives bladder cancer metastasis. This may be modulated through alterations in intracellular signaling and cellular adhesion. FOXF1 may serve as a prognostic biomarker that can identify patients at impending risk for metastasis who may benefit from more aggressive management.

Sign in / Sign up

Export Citation Format

Share Document