دورية أكاديمية
Mtbp haploinsufficiency in mice increases tumor metastasis.
| العنوان: | Mtbp haploinsufficiency in mice increases tumor metastasis. |
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| المؤلفون: | Iwakuma T; Department of Genetics, Louisiana State University Health Science Center, New Orleans, LA 70112, USA. tiwaku@lsuhsc.edu, Tochigi Y, Van Pelt CS, Caldwell LC, Terzian T, Parant JM, Chau GP, Koch JG, Eischen CM, Lozano G |
| المصدر: | Oncogene [Oncogene] 2008 Mar 20; Vol. 27 (13), pp. 1813-20. Date of Electronic Publication: 2007 Oct 01. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8711562 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5594 (Electronic) Linking ISSN: 09509232 NLM ISO Abbreviation: Oncogene Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2002->: Basingstoke : Nature Publishing Group Original Publication: Basingstoke, Hampshire, UK : Scientific & Medical Division, MacMillan Press, c1987- |
| مواضيع طبية MeSH: | Bone Neoplasms/*pathology , Carrier Proteins/*physiology , Liver Neoplasms/*secondary , Osteosarcoma/*secondary, Animals ; Blotting, Southern ; Bone Neoplasms/metabolism ; Cell Movement ; Female ; Gene Silencing/physiology ; Liver Neoplasms/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Neoplasm Invasiveness ; Osteosarcoma/metabolism ; Phenotype ; Pregnancy ; Proto-Oncogene Proteins c-mdm2/metabolism ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Suppressor Protein p53/metabolism |
| مستخلص: | Mdm2 inhibits the function of the p53 tumor suppressor. Mdm2 is overexpressed in many tumors with wild-type p53 suggesting an alternate mechanism of loss of p53 activity in tumors. An Mdm2-binding protein (MTBP) was identified using a yeast two-hybrid screen. In tissue culture, MTBP inhibits Mdm2 self-ubiquitination, leading to stabilization of Mdm2 and increased degradation of p53. To address the role of MTBP in the regulation of the p53 pathway in vivo, we deleted the Mtbp gene in mice. Homozygous disruption of Mtbp resulted in early embryonic lethality, which was not rescued by loss of p53. Mtbp+/- mice were not tumor prone. When mice were sensitized for tumor development by p53 heterozygosity, we found that the Mtbp+/-p53+/- mice developed significantly more metastatic tumors (18.2%) as compared to p53+/- mice (2.6%). Results of in vitro migration and invasion assays support the in vivo findings. Downmodulation of Mtbp in osteosarcoma cells derived from p53+/- mice resulted in increased invasiveness, and overexpression of Mtbp in Mtbp+/-p53+/- osteosarcoma cells inhibited invasiveness. These results suggest that MTBP is a metastasis suppressor. These results advance our understanding of the cellular roles of MTBP and raise the possibility that MTBP is a novel therapeutic target for metastasis. |
| معلومات مُعتمدة: | CA098139 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (Carrier Proteins) 0 (Mtbp protein, mouse) 0 (RNA, Messenger) 0 (Tumor Suppressor Protein p53) EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2) |
| تواريخ الأحداث: | Date Created: 20071002 Date Completed: 20080408 Latest Revision: 20220321 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1038/sj.onc.1210827 |
| PMID: | 17906694 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1476-5594 |
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| DOI: | 10.1038/sj.onc.1210827 |