The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
A Novel Somatic Mouse Model to Survey Tumorigenic Potential Applied to the Hedgehog Pathway
Open accessAbstract
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. (Cancer Res 2006; 66(20): 10171-7)
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Cites
Gli2, but not Gli1, is required for initial Shh signaling and ectopic activation of the Shh pathway
Bai, C. B., Auerbach, W., Lee, J. S., Stephen, D., & Joyner, A. L. (2002) · Development · doi:10.1242/dev.129.20.4753 · Cited by 692
Cited by
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Rhim, A. D., Oberstein, P. E., Thomas, D. H., Mirek, E. T., Palermo, C. F., Sastra, S. A., Dekleva, E. N., Saunders, T., Becerra, C. P., Tattersall, I. W., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.04.021 · Cited by 2,085
Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia
Zhao, C., Chen, A., Jamieson, C. H., Fereshteh, M., Abrahamsson, A., Blum, J., Kwon, H. Y., Kim, J., Chute, J. P., Rizzieri, D., et al. (2009) · Nature · doi:10.1038/nature07737 · Cited by 869
Schüller, U., Heine, V. M., Mao, J., Kho, A. T., Dillon, A. K., Han, Y.-G., Huillard, E., Sun, T., Ligon, A. H., Qian, Y., et al. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.07.005 · Cited by 667
Self-citationNorthcott, P. A., Robinson, G. W., Kratz, C. P., Mabbott, D. J., Pomeroy, S. L., Clifford, S. C., Rutkowski, S., Ellison, D. W., Malkin, D., Taylor, M. D., et al. (2019) · Nature Reviews Disease Primers · doi:10.1038/s41572-019-0063-6 · Cited by 649
KRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma
Morris, J. P., Wang, S. C., & Hebrok, M. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2899 · Cited by 567
Metadata
- Authors
- Mao, J., Ligon, K. L., Rakhlin, E. Y., Thayer, S. P., Bronson, R. T., Rowitch, D., & McMahon, A. P.
- Venue
- Cancer Research
- Published
- 2006-10-15
- Volume
- 66
- Issue
- 20
- Pages
- 10171-10178
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2099167893
- Cited by
- 296
- References
- 1
- FWCI
- 3.32
- Type
- journal article
- Language
- en
- Open access
- green
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- Mao, J., Ligon, K. L., Rakhlin, E. Y., Thayer, S. P., Bronson, R. T., Rowitch, D., & McMahon, A. P. (2006). A Novel Somatic Mouse Model to Survey Tumorigenic Potential Applied to the Hedgehog Pathway. Cancer Research. https://doi.org/10.1158/0008-5472.can-06-0657
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