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| Status |
Public on Jul 28, 2021 |
| Title |
mRNA expression profiling of untreated J82 and MDXC1 cultured cell lines using the Nanostring PanCancer Progression 770 gene panel |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
J82 is a urothelial carcinoma (bladder cancer) derived cultured cell line (see COSMIC https://cancer.sanger.ac.uk/cosmic/sample/overview?id=753566). The cultured cell line MDXC1 was derived from J82 xenograft tumors grown in SCID/BEIGE mice for 50 days using conventional methods of tumor excision, cell dissociation and growth in culture for 15 passages. MDXC1 was confirmed to be solely of human origin and pathogen-free.
J82 and MDXC1 cells were compared for phenotypic changes in cancer-related genes associated with xenograft tumor growth. Experiments were included in the following larger study: Title: Autocrine signaling by receptor tyrosine kinases in urothelial carcinoma of the bladder. Authors: Young H. Lee, Molly M. Lee, Dinuka M. De Silva, Arpita Roy, Cara Wright, Tiffany Wong, Rene Costello, Oluwole Olaku, Robert L. Grubb III#, Piyush K. Agarwal, Andrea B. Apolo*+ Donald P. Bottaro* Affiliations: Urologic Oncology Branch and +Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 USA and #Department of Urology, Medical University of South Carolina, Charleston, South Carolina 29425 USA Abstract: Comprehensive characterizations of bladder cancer (BCa) have established molecular phenotype classes with distinct alterations and survival trends. Extending these studies within the tyrosine kinase (TK) family to identify disease drivers could improve our use of TK inhibitors to treat specific patient groups or individuals. We examined the expression distribution of TKs as a class (n = 89) in The Cancer Genome Atlas (TCGA) muscle invasive BCa data set (n >400). Patient profiles of potentially oncogenic alterations (overexpression and/or amplification) clustered TKs into 3 groups; alterations of group 1 and 3 TKs were associated with significantly worse patient survival relative to those without alterations. Many TK pathways induce epithelial-to-mesenchymal transition (EMT), which promotes tumor invasiveness and metastasis. Overexpression and/or amplification among 9 EMT transcriptional activators occurred in 43% of TCGA cases. Co-occurring alterations of TKs and EMT transcriptional activators involved most group 1 TKs; 24% of these events were associated with significantly worse patient survival. Co-occurring alterations of receptor TKs and their cognate ligands occurred in 16% of TCGA cases and several BCa-derived cell lines. Suppression of GAS6, MST1 or CSF1, or their respective receptors (AXL, MST1R and CSF1R), in BCa cell lines was associated with decreased receptor activation, cell migration, cell proliferation and anchorage independent cell growth. These studies reveal the patterns and prevalence of potentially oncogenic TK pathway-related alterations in BCa and identify specific alterations associated with reduced BCa patient survival. Detection of these features in BCa patients could better inform TK inhibitor use and improve clinical outcomes.
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| Overall design |
Cell lines were grown under identical plating and culture conditions prior to harvest and RNA extraction and hybridization.
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| Contributor(s) |
Bottaro DP, Costello R, De Silva D, Roy A, Lee M |
| Citation(s) |
34292953 |
| Submission date |
Aug 17, 2020 |
| Last update date |
Jul 29, 2021 |
| Contact name |
Donald P Bottaro |
| E-mail(s) |
dbottaro@helix.nih.gov
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| Organization name |
National Cancer Institute
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| Department |
Center for Cancer Research
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| Lab |
Urologic Oncology Branch
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| Street address |
Bldg 10 CRC Rm 2-3952, 10 Center Drive
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL23845 |
nCounter PanCancer Progression panel |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA657574 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE156348_RAW.tar |
40.0 Kb |
(http)(custom) |
TAR (of RCC) |
| Processed data included within Sample table |
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