Please use this identifier to cite or link to this item:
http://hdl.handle.net/10397/5618
| Title: | Conditional inactivation of Pten with EGFR overexpression in Schwann cells models sporadic MPNST | Authors: | Keng, WKV Watson, AL Rahrmann, EP Li, H Tschida, BR Moriarity, BS Choi, K Rizvi, TA Collins, MH Wallace, MR Ratner, N Largaespada, DA |
Issue Date: | 2012 | Source: | Sarcoma, v. 2012 (620834), p. 1-12 | Abstract: | The genetic mechanisms involved in the transformation from a benign neurofibroma to a malignant sarcoma in patients with neurofibromatosis-type-1- (NF1-)associated or sporadic malignant peripheral nerve sheath tumors (MPNSTs) remain unclear. It is hypothesized that many genetic changes are involved in transformation. Recently, it has been shown that both phosphatase and tensin homolog (PTEN) and epidermal growth factor receptor (EGFR) play important roles in the initiation of peripheral nerve sheath tumors (PNSTs). In human MPNSTs, PTEN expression is often reduced, while EGFR expression is often induced. We tested if these two genes cooperate in the evolution of PNSTs. Transgenic mice were generated carrying conditional floxed alleles of Pten, and EGFR was expressed under the control of the 2′,3′-cyclic nucleotide 3′phosphodiesterase (Cnp) promoter and a desert hedgehog (Dhh) regulatory element driving Cre recombinase transgenic mice (Dhh-Cre). Complete loss of Pten and EGFR overexpression in Schwann cells led to the development of high-grade PNSTs. In vitro experiments using immortalized human Schwann cells demonstrated that loss of PTEN and overexpression of EGFR cooperate to increase cellular proliferation and anchorage-independent colony formation. This mouse model can rapidly recapitulate PNST onset and progression to high-grade PNSTs, as seen in sporadic MPNST patients. | Keywords: | Animal cell Animal experiment Animal model Gene overexpression Cell proliferation Colony formation Controlled study Enzyme inactivation Nerve sheath tumor Peripheral nerve sheath tumor Protein depletion Schwann cell |
Publisher: | Hindawi Publishing Corporation | Journal: | Sarcoma | ISSN: | 1357-714X | DOI: | 10.1155/2012/620834 | Rights: | Copyright © 2012 Vincent W. Keng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Appears in Collections: | Journal/Magazine Article |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| Keng_2012_Sarcoma[1].pdf | 3.62 MB | Adobe PDF | View/Open |
Access
View full-text via PolyU eLinks 
Page views
79
Last Week
0
0
Last month
Citations as of Jun 4, 2023
Downloads
107
Citations as of Jun 4, 2023
SCOPUSTM
Citations
26
Last Week
0
0
Last month
0
0
Citations as of Jun 8, 2023
Google ScholarTM
Check
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.