Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas-a possible mechanism for altering the nm23-H1 activity.

Détails

ID Serval
serval:BIB_D4E69DCF698F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas-a possible mechanism for altering the nm23-H1 activity.
Périodique
Oncogene
Auteur(s)
Forus A., D'Angelo A., Henriksen J., Merla G., Maelandsmo G.M., Flørenes V.A., Olivieri S., Bjerkehagen B., Meza-Zepeda L.A., del Vecchio Blanco F., Müller C., Sanvito F., Kononen J., Nesland J.M., Fodstad Ø., Reymond A., Kallioniemi O.P., Arrigoni G., Ballabio A., Myklebost O., Zollo M.
ISSN
0950-9232[print], 0950-9232[linking]
Statut éditorial
Publié
Date de publication
2001
Volume
20
Numéro
47
Pages
6881-6890
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
PRUNE, the human homologue of the Drosophila gene, is located in 1q21.3, a region highly amplified in human sarcomas, malignant tumours of mesenchymal origin. Prune protein interacts with the metastasis suppressor nm23-H1, but shows impaired affinity towards the nm23-H1 S120G mutant associated with advanced neuroblastoma. Based on these observations, we previously suggested that prune may act as a negative regulator of nm23-H1 activity. We found amplification of PRUNE in aggressive sarcoma subtypes, such as leiomyosarcomas and malignant fibrous histiocytomas (MFH) as well as in the less malignant liposarcomas. PRUNE amplification was generally accompanied by high mRNA and moderate to high protein levels. The sarcoma samples expressed nm23-H1 mostly at low or moderate levels, whereas mRNA and protein levels were moderate to high in breast carcinomas. For the more aggressive sarcoma subtypes, 9/13 patients with PRUNE amplification developed metastases. A similar situation was observed in all breast carcinomas with amplification of PRUNE. Infection of NIH3T3 cells with a PRUNE recombinant retrovirus increased cell proliferation. Possibly, amplification and overexpression of PRUNE has the same effect in the tumours. We suggest that amplification and overexpression of PRUNE could be a mechanism for inhibition of nm23-H1 activity that affect the development or progression of these tumours.
Mots-clé
3T3 Cells, Animals, Breast Neoplasms/genetics, Breast Neoplasms/pathology, COS Cells, Carcinoma/genetics, Carcinoma/pathology, Carrier Proteins/genetics, Carrier Proteins/physiology, Cell Division, Drosophila Proteins, Female, Gene Amplification, Gene Expression Regulation, Neoplastic, Humans, Insect Proteins/genetics, Insect Proteins/physiology, Mice, Monomeric GTP-Binding Proteins/genetics, Monomeric GTP-Binding Proteins/metabolism, NM23 Nucleoside Diphosphate Kinases, Neoplasm Metastasis, Nucleoside-Diphosphate Kinase, RNA, Neoplasm/biosynthesis, Sarcoma/genetics, Sarcoma/pathology, Transcription Factors/genetics, Transcription Factors/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
11/05/2009 12:49
Dernière modification de la notice
20/08/2019 16:54
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