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| Status |
Public on Sep 06, 2013 |
| Title |
Global gene expression profiling of mesotheliomas from vehicle control and VDC-exposed male F344N rats |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
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| Summary |
A recent two-year NTP cancer bioassay showed a marked increase in the incidence of malignant mesothelioma arising from the tunica vaginalis in male Fischer 344/N rats exposed to Vinylidene chloride (VDC). Aged male F344/N rats are prone to developing spontaneous peritoneal mesotheliomas, which also arise predominantly from the tunica vaginalis of the testes. A definitive mechanism for the observed increased incidence in VDC-exposed rats is unknown. Investigation of the molecular alterations that occur in mesotheliomas from vehicle control and VDC-exposed rats may provide insight into their pathogenesis, as well enable a better understanding regarding the mechanisms underlying chemically induced mesothelioma in rodents. Mesothelial cell function represents a complex interplay of pathways related to host defense mechanisms and maintenance of cellular homeostasis. Global gene expression profiles of spontaneous mesotheliomas from vehicle control male F344/N rats from various two-year National Toxicology Program carcinogenicity bioassays were compared to mesotheliomas from VDC-exposed rats to characterize the molecular features that are present in mesotheliomas from VDC-exposed animals, and to elucidate tumor-specific gene expression profiles. The resulting gene expression pattern showed that mesotheliomas from VDC-exposed animals are genomically very different from spontaneous tumors; while both tumor types are characterized by alterations in gene expression associated with carcinogenic pathways (oncogenes, tumor suppressor genes, growth factors, etc.), mesotheliomas from VDC-exposed animals are associated with increased dysreguation of immune pathways and inflammatory mediators. Alterations in these pathways may suggest a pro-inflammatory and immune dysfunction signature as one mechanism in the observed increased incidence of these tumors in VDC-exposed animals.
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| Overall design |
Five spontaneous malignant mesotheliomas from two-year-old F344/N rats, eight mesotheliomas from VDC-exposed two-year-old F344/N rats, and six normal Fred-PE mesothelial cell culture samples (as controls).
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| Contributor(s) |
Blackshear P, Pandiri AR, Ton T, Clayton NP, Shockley KR, Peddada SD, Gerrish KE, Sills RC, Hoenerhoff MJ |
| Citation(s) |
23980201, 24958746 |
| Submission date |
May 31, 2013 |
| Last update date |
Jul 31, 2017 |
| Contact name |
NIEHS Microarray Core |
| E-mail(s) |
microarray@niehs.nih.gov, liuliw@niehs.nih.gov
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| Organization name |
NIEHS
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| Department |
DIR
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| Lab |
Microarray Core
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| Street address |
111 T.W. Alexander Drive
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| City |
RTP |
| State/province |
NC |
| ZIP/Postal code |
27709 |
| Country |
USA |
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| Platforms (1) |
| GPL1355 |
[Rat230_2] Affymetrix Rat Genome 230 2.0 Array |
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| Samples (19)
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| Relations |
| BioProject |
PRJNA206191 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE47581_RAW.tar |
55.1 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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