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A spatially and temporally restricted mouse model of soft tissue sarcoma.

Publication ,  Journal Article
Kirsch, DG; Dinulescu, DM; Miller, JB; Grimm, J; Santiago, PM; Young, NP; Nielsen, GP; Quade, BJ; Chaber, CJ; Schultz, CP; Takeuchi, O ...
Published in: Nature medicine
August 2007

Soft tissue sarcomas are mesenchymal tumors that are fatal in approximately one-third of patients. To explore mechanisms of sarcoma pathogenesis, we have generated a mouse model of soft tissue sarcoma. Intramuscular delivery of an adenovirus expressing Cre recombinase in mice with conditional mutations in Kras and Trp53 was sufficient to initiate high-grade sarcomas with myofibroblastic differentiation. Like human sarcomas, these tumors show a predilection for lung rather than lymph node metastasis. Using this model, we showed that a prototype handheld imaging device can identify residual tumor during intraoperative molecular imaging. Deletion of the Ink4a-Arf locus (Cdkn2a), but not Bak1 and Bax, could substitute for mutation of Trp53 in this model. Deletion of Bak1 and Bax, however, was able to substitute for mutation of Trp53 in the development of sinonasal adenocarcinoma. Therefore, the intrinsic pathway of apoptosis seems sufficient to mediate p53 tumor suppression in an epithelial cancer, but not in this model of soft tissue sarcoma.

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Published In

Nature medicine

DOI

EISSN

1546-170X

ISSN

1078-8956

Publication Date

August 2007

Volume

13

Issue

8

Start / End Page

992 / 997

Related Subject Headings

  • Up-Regulation
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Protein p14ARF
  • Time Factors
  • Sarcoma
  • Mice, Knockout
  • Mice
  • Lung Neoplasms
  • Immunology
  • Gene Expression Regulation, Neoplastic
 

Citation

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Kirsch, D. G., Dinulescu, D. M., Miller, J. B., Grimm, J., Santiago, P. M., Young, N. P., … Jacks, T. (2007). A spatially and temporally restricted mouse model of soft tissue sarcoma. Nature Medicine, 13(8), 992–997. https://doi.org/10.1038/nm1602
Kirsch, David G., Daniela M. Dinulescu, John B. Miller, Jan Grimm, Philip M. Santiago, Nathan P. Young, G Petur Nielsen, et al. “A spatially and temporally restricted mouse model of soft tissue sarcoma.Nature Medicine 13, no. 8 (August 2007): 992–97. https://doi.org/10.1038/nm1602.
Kirsch DG, Dinulescu DM, Miller JB, Grimm J, Santiago PM, Young NP, et al. A spatially and temporally restricted mouse model of soft tissue sarcoma. Nature medicine. 2007 Aug;13(8):992–7.
Kirsch, David G., et al. “A spatially and temporally restricted mouse model of soft tissue sarcoma.Nature Medicine, vol. 13, no. 8, Aug. 2007, pp. 992–97. Epmc, doi:10.1038/nm1602.
Kirsch DG, Dinulescu DM, Miller JB, Grimm J, Santiago PM, Young NP, Nielsen GP, Quade BJ, Chaber CJ, Schultz CP, Takeuchi O, Bronson RT, Crowley D, Korsmeyer SJ, Yoon SS, Hornicek FJ, Weissleder R, Jacks T. A spatially and temporally restricted mouse model of soft tissue sarcoma. Nature medicine. 2007 Aug;13(8):992–997.

Published In

Nature medicine

DOI

EISSN

1546-170X

ISSN

1078-8956

Publication Date

August 2007

Volume

13

Issue

8

Start / End Page

992 / 997

Related Subject Headings

  • Up-Regulation
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Protein p14ARF
  • Time Factors
  • Sarcoma
  • Mice, Knockout
  • Mice
  • Lung Neoplasms
  • Immunology
  • Gene Expression Regulation, Neoplastic