Source:http://linkedlifedata.com/resource/pubmed/id/17230190
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7129
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| pubmed:dateCreated |
2007-2-15
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| pubmed:abstractText |
Mice of the C57BL/6 strain are resistant to the development of skin squamous carcinomas (SCCs) induced by an activated Ras oncogene, whereas FVB/N mice are highly susceptible. The genetic basis of this difference in phenotype is unknown. Here we show that susceptibility to SCC is under the control of a carboxy-terminal polymorphism in the mouse Ptch gene. F1 hybrids between C57BL/6 and FVB/N strains ((B6FVB)F1) are resistant to Ras-induced SCCs, but resistance can be overcome either by elimination of the C57BL/6 Ptch allele (Ptch(B6)) or by overexpression of the FVB/N Ptch allele (Ptch(FVB)) in the epidermis of K5Hras-transgenic (B6FVB)F1 hybrid mice. The human Patched (PTCH) gene is a classical tumour suppressor gene for basal cell carcinomas and medulloblastomas, the loss of which causes increased signalling through the Sonic Hedgehog (SHH) pathway. SCCs that develop in PtchB6+/- mice do not lose the wild-type Ptch gene or show evidence of increased SHH signalling. Although Ptch(FVB) overexpression can promote SCC formation, continued expression is not required for tumour maintenance, suggesting a role at an early stage of tumour cell lineage commitment. The Ptch polymorphism affects Hras-induced apoptosis, and binding to Tid1, the mouse homologue of the Drosophila l(2)tid tumour suppressor gene. We propose that Ptch occupies a critical niche in determining basal or squamous cell lineage, and that both tumour types can arise from the same target cell depending on carcinogen exposure and host genetic background.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Dnaja3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Gli2 protein,
http://linkedlifedata.com/resource/pubmed/chemical/HSP40 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Kruppel-Like Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/patched receptors,
http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins
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| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
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| pubmed:issn |
1476-4687
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
15
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| pubmed:volume |
445
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
761-5
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| pubmed:meshHeading |
pubmed-meshheading:17230190-Amino Acid Sequence,
pubmed-meshheading:17230190-Animals,
pubmed-meshheading:17230190-Apoptosis,
pubmed-meshheading:17230190-Carcinoma, Squamous Cell,
pubmed-meshheading:17230190-Cell Line,
pubmed-meshheading:17230190-Cell Transformation, Neoplastic,
pubmed-meshheading:17230190-Crosses, Genetic,
pubmed-meshheading:17230190-Female,
pubmed-meshheading:17230190-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:17230190-Genes, ras,
pubmed-meshheading:17230190-HSP40 Heat-Shock Proteins,
pubmed-meshheading:17230190-Humans,
pubmed-meshheading:17230190-Kruppel-Like Transcription Factors,
pubmed-meshheading:17230190-Male,
pubmed-meshheading:17230190-Mice,
pubmed-meshheading:17230190-Mice, Inbred C57BL,
pubmed-meshheading:17230190-Mice, Transgenic,
pubmed-meshheading:17230190-Molecular Sequence Data,
pubmed-meshheading:17230190-Polymorphism, Genetic,
pubmed-meshheading:17230190-Receptors, Cell Surface,
pubmed-meshheading:17230190-ras Proteins
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| pubmed:year |
2007
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| pubmed:articleTitle |
Promotion of Hras-induced squamous carcinomas by a polymorphic variant of the Patched gene in FVB mice.
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| pubmed:affiliation |
Cancer Research Institute, University of California at San Francisco, 2340 Sutter Street, San Francisco, California 94143, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
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