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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 19, 2019 |
| Title |
Expression data in Fhit-negative cell lines |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Characterizing signal pathway alterations that contribute to cellular transformation induced by loss of Fhit protein
Abstract: The FHIT gene, encompassing an active common fragile site, FRA3B, is frequently silenced in preneoplasia and cancer, through gene rearrangement or methylation of regulatory sequences. Silencing of Fhit protein expression causes thymidine kinase 1 downregulation, resulting in dNTP imbalance, and spontaneous replication stress that leads to chromosomal aberrations, allele copy number variations, insertions/deletions, and single‐base substitutions. Thus, Fhit, which is reduced in expression in the majority of human cancers, is a genome “caretaker” whose loss initiates genome instability in preneoplastic lesions. To follow the early genetic alterations and functional changes induced by Fhit loss that may recapitulate the neoplastic process in vitro, we established epithelial cell lines from kidney tissues of Fhit−/− and +/+ mouse pups early after weaning, and subjected cell cultures to nutritional and carcinogen stress, which +/+ cells did not survive. Through transcriptome profiling and protein expression analysis, we observed changes in the Trp53/p21 and survivin apoptotic pathways in −/− cells, and in expression of proteins involved in epithelial–mesenchymal transition. Some Fhit‐deficient cell lines showed anchorage‐independent colony formation and increased invasive capacity in vitro. Furthermore, cells of stressed Fhit−/− cell lines formed s.c. and metastatic tumors in nude mice. Collectively, we show that Fhit loss and subsequent thymidine kinase 1 inactivation, combined with selective pressures, leads to neoplasia‐associated alterations in genes and gene expression patterns in vitro and in vivo.
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| Overall design |
mouse kidney epithelial cell lines were derived from fhit knockout mice and subcultured with and without carcinogenic and nutritional stress
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| Contributor(s) |
Huebner K |
| Citation(s) |
27513973 |
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| Submission date |
Jul 18, 2019 |
| Last update date |
Jul 21, 2019 |
| Contact name |
Kay Huebner |
| Organization name |
The Ohio State University
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| Street address |
460 W. 12th Ave
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| City |
Columbus |
| ZIP/Postal code |
43210 |
| Country |
USA |
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| Platforms (1) |
| GPL20775 |
[MTA-1_0] Affymetrix Mouse Transcriptome Array 1.0 [transcript (gene) CSV version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA555253 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE134478_RAW.tar |
152.8 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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