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Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas-a possible mechanism for altering the nm23-H1 activity.
- Source :
-
Oncogene [Oncogene] 2001 Oct 18; Vol. 20 (47), pp. 6881-90. - Publication Year :
- 2001
-
Abstract
- 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.
- Subjects :
- 3T3 Cells
Animals
Breast Neoplasms pathology
COS Cells
Carcinoma pathology
Carrier Proteins physiology
Cell Division
Female
Humans
Insect Proteins physiology
Mice
Monomeric GTP-Binding Proteins genetics
NM23 Nucleoside Diphosphate Kinases
Neoplasm Metastasis
Phosphoric Monoester Hydrolases
RNA, Neoplasm biosynthesis
Sarcoma pathology
Transcription Factors genetics
Breast Neoplasms genetics
Carcinoma genetics
Carrier Proteins genetics
Drosophila Proteins
Gene Amplification
Gene Expression Regulation, Neoplastic
Insect Proteins genetics
Monomeric GTP-Binding Proteins metabolism
Nucleoside-Diphosphate Kinase
Sarcoma genetics
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0950-9232
- Volume :
- 20
- Issue :
- 47
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 11687967
- Full Text :
- https://doi.org/10.1038/sj.onc.1204874