A novel somatic mouse model to survey tumorigenic potential applied to the Hedgehog pathway.

A novel somatic mouse model to survey tumorigenic potential applied to the Hedgehog pathway. Research Abstract Details 

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A novel somatic mouse model to survey tumorigenic potential applied to the Hedgehog pathway. Abstract Text:

Junhao Mao,Keith L Ligon,Elena Y Rakhlin,Sarah P Thayer,Roderick T Bronson,David Rowitch,Andrew P McMahon,

We report a novel mouse model for the generation of sporadic tumors and show the efficiency of this approach by surveying Hedgehog (Hh)-related tumors. Up-regulation of the Hh pathway is achieved by conditionally regulated expression of an activated allele of Smoothened (R26-SmoM2) using either sporadic leakage or global postnatal induction of a ubiquitously expressed inducible Cre transgene (CAGGS-CreER). Following postnatal tamoxifen induction, CAGGS-CreER; R26-SmoM2 mice developed tumors with short latency and high penetrance. All mice exhibited rhabdomyosarcoma and basal cell carcinoma; 40% also developed medulloblastoma. In addition, mice showed a novel pancreatic lesion resembling low-grade mucinous cystic neoplasms in humans. In contrast, widespread activation of SmoM2 in the postnatal prostate epithelium results in no detectable morphologic outcome in 12-month-old mice. Comparison of gene expression profiles among diverse tumors identified several signature genes, including components of platelet-derived growth factor and insulin-like growth factor pathways, which may provide a common mechanistic link to the Hh-related malignancies. This experimental model provides a robust tool for exploring the process of Hh-dependent tumorigenesis and the treatment of such tumors. More generally, this approach provides a genetic platform for identifying tumorigenic potential in putative oncogenes and tumor suppressors and for more effective modeling of sporadic cancers in mice.

A novel somatic mouse model to survey tumorigenic potential applied to the Hedgehog pathway. Publishing Authors By Initials

J Mao,KL Ligon,EY Rakhlin,SP Thayer,RT Bronson,D Rowitch,AP McMahon,

For similar neoplasms: neoplasms by site: skin neoplasms research abstracts see: neoplasms: neoplasms by site: skin neoplasms research

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A novel somatic mouse model to survey tumorigenic potential applied to the Hedgehog pathway. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Cancer research

VOLUME: 66

Page Numbers: 10171-8

Journal Abbreviation: Cancer Res.

ISSN: 0008-5472

DAY: 15

MONTH: Oct

YEAR: 2006

A novel somatic mouse model to survey tumorigenic potential applied to the Hedgehog pathway. Information

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LANGUAGE: eng

NlmUniqueID: 2984705

A novel somatic mouse model to survey tumorigenic potential applied to the Hedgehog pathway. Keywords Mesh Terms:

KEYWORDS: Skin Neoplasms

MESH TERMS: pathology

Chemical & Substance for Abstract: A novel somatic mouse model to survey tumorigenic potential applied to the Hedgehog pathway. Information

Substance Name: Integrases

Registry Number: EC 2.7.7.-

Grant and Affiliation Information for A novel somatic mouse model to survey tumorigenic potential applied to the Hedgehog pathway.

AFFILIATION: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.

Country: United States

AGENCY: United States NINDS

GRANT: R37-NS033642

ACRONYM: NS

MEDLINETA: Cancer Res

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