Description
Accession Number: GSE42103
Platform:
GPL1261: [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Organism: Mus musculus
Published on 2013-01-01
Summary:
Soft tissue sarcomas (STS) are a heterogeneous group of tumors associated with poor clinical outcome. While a subset of STS are characterized by simple karyotypes and recurrent chromosomal translocations, the mechanisms driving cytogenetically complex sarcomas are largely unknown. Clinical evidence led us to partially inactivate Pten and p53 in the smooth muscle lineage of mice, which developed high-grade undifferentiated pleomorphic sarcomas (HGUPS), leiomyosarcomas (LMS) and carcinosarcomas (CS) that widely recapitulate the human disease, including the aberrant karyotype and metastatic behavior. Pten was found haploinsufficient whereas the wild-type allele of p53 invariably gained point mutations. Gene expression profile showed upregulated Notch signaling in Pten∆/+p53∆/+ tumors compared to Pten+/+p53∆/+. Consistently, Pten silencing exacerbated the clonogenic and invasive potential of p53-deficient bone marrow-derived mouse mesenchymal stem cells and tumor cells, while activating the Notch pathway. Moreover, the increased oncogenic behavior of Pten∆/+p53∆/+ and shPten-transduced Pten+/+p53∆/+ tumor cells was counteracted by treatment with a gamma secretase inhibitor (GSI), suggesting that the aggressiveness of those tumors can be attributed, at least in part, to enhanced Notch signaling. This study demonstrates a cooperative role for Pten and p53 suppression in complex karyotype sarcomas while establishing Notch as an important functional player in the crosstalk of these pathways during tumor progression. Our results highlight the importance of molecularly subclassifying high-grade sarcoma patients for targeted treatments. Compare Pten∆/+p53∆/+ to Pten+/+p53∆/+ high-grade undifferentiated pleomorphic sarcomas (HGUPS)
Overall Design:
4 Pten∆/+p53∆/+ were compared to 5 Pten+/+p53∆/+ Keywords: Differential gene expression.
Contact:
Name: Jiri Zavadil
Organization: NYU SoM
Deparment: Pathology
Address: 550 First Ave New York NY 10016 USA
Email: [email protected]
Phone: 212-263-8048
Organization: Affymetrix, Inc.
Address: Santa Clara CA 95051 USA
Email: [email protected], [email protected]
Phone: 888-362-2447
Web-Link: http://www.affymetrix.com/index.affx
Platform:
GPL1261: [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Organism: Mus musculus
Published on 2013-01-01
Summary:
Soft tissue sarcomas (STS) are a heterogeneous group of tumors associated with poor clinical outcome. While a subset of STS are characterized by simple karyotypes and recurrent chromosomal translocations, the mechanisms driving cytogenetically complex sarcomas are largely unknown. Clinical evidence led us to partially inactivate Pten and p53 in the smooth muscle lineage of mice, which developed high-grade undifferentiated pleomorphic sarcomas (HGUPS), leiomyosarcomas (LMS) and carcinosarcomas (CS) that widely recapitulate the human disease, including the aberrant karyotype and metastatic behavior. Pten was found haploinsufficient whereas the wild-type allele of p53 invariably gained point mutations. Gene expression profile showed upregulated Notch signaling in Pten∆/+p53∆/+ tumors compared to Pten+/+p53∆/+. Consistently, Pten silencing exacerbated the clonogenic and invasive potential of p53-deficient bone marrow-derived mouse mesenchymal stem cells and tumor cells, while activating the Notch pathway. Moreover, the increased oncogenic behavior of Pten∆/+p53∆/+ and shPten-transduced Pten+/+p53∆/+ tumor cells was counteracted by treatment with a gamma secretase inhibitor (GSI), suggesting that the aggressiveness of those tumors can be attributed, at least in part, to enhanced Notch signaling. This study demonstrates a cooperative role for Pten and p53 suppression in complex karyotype sarcomas while establishing Notch as an important functional player in the crosstalk of these pathways during tumor progression. Our results highlight the importance of molecularly subclassifying high-grade sarcoma patients for targeted treatments. Compare Pten∆/+p53∆/+ to Pten+/+p53∆/+ high-grade undifferentiated pleomorphic sarcomas (HGUPS)
Overall Design:
4 Pten∆/+p53∆/+ were compared to 5 Pten+/+p53∆/+ Keywords: Differential gene expression.
Contact:
Name: Jiri Zavadil
Organization: NYU SoM
Deparment: Pathology
Address: 550 First Ave New York NY 10016 USA
Email: [email protected]
Phone: 212-263-8048
Organization: Affymetrix, Inc.
Address: Santa Clara CA 95051 USA
Email: [email protected], [email protected]
Phone: 888-362-2447
Web-Link: http://www.affymetrix.com/index.affx
| Date made available | Nov 7 2012 |
|---|---|
| Publisher | Gene Expression Omnibus |