| Title |
Spatially- and temporally-controlled postnatal p53 knockdown cooperates with embryonic Schwann cell precursor Nf1 gene loss to promote malignant peripheral nerve sheath tumor formation
|
|---|---|
| Published in |
Oncotarget, February 2016
|
| DOI | 10.18632/oncotarget.7232 |
| Pubmed ID | |
| Authors |
Angela C. Hirbe, Sonika Dahiya, Dinorah Friedmann-Morvinski, Inder M. Verma, D. Wade Clapp, David H. Gutmann |
| Abstract |
Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive sarcomas that arise sporadically or in association with the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome. In individuals with NF1, MPNSTs are hypothesized to arise from Nf1-deficient Schwann cell precursor cells following the somatic acquisition of secondary cooperating genetic mutations (e.g., p53 loss). To model this sequential genetic cooperativity, we coupled somatic lentivirus-mediated p53 knockdown in the adult right sciatic nerve with embryonic Schwann cell precursor Nf1 gene inactivation in two different Nf1 conditional knockout mouse strains. Using this approach, ~60% of mice with Periostin-Cre-mediated Nf1 gene inactivation (Periostin-Cre; Nf1flox/flox mice) developed tumors classified as low-grade MPNSTs following p53 knockdown (mean, 6 months). Similarly, ~70% of Nf1+/- mice with GFAP-Cre-mediated Nf1 gene inactivation (GFAP-Cre; Nf1flox/null mice) developed low-grade MPNSTs following p53 knockdown (mean, 3 months). In addition, wild-type and Nf1+/- mice with GFAP-Cre-mediated Nf1 loss develop MPNSTs following somatic p53 knockout with different latencies, suggesting potential influences of Nf1+/- stromal cells in MPNST pathogenesis. Collectively, this new MPNST model system permits the analysis of somatically-acquired events as well as tumor microenvironment signals that potentially cooperate with Nf1 loss in the development and progression of this deadly malignancy. |
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 1 | 3% |
| Unknown | 31 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 7 | 22% |
| Researcher | 5 | 16% |
| Other | 3 | 9% |
| Student > Ph. D. Student | 2 | 6% |
| Student > Bachelor | 1 | 3% |
| Other | 3 | 9% |
| Unknown | 11 | 34% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 8 | 25% |
| Medicine and Dentistry | 5 | 16% |
| Agricultural and Biological Sciences | 4 | 13% |
| Computer Science | 2 | 6% |
| Psychology | 1 | 3% |
| Other | 1 | 3% |
| Unknown | 11 | 34% |
Attention Score in Context
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#18,345,259
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#7,902
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