MITOSTATIN, a putative tumor suppressor on chromosome 12q24.1, is downregulated in human bladder and breast cancer
| Autor: | Vecchione, A., Fassan, M., Anesti, V., Morrione, A., Goldoni, S., Baldassarre, G., Byrne, D., D'Arca, D., Palazzo, J. P., Lloyd, J., Scorrano, Luca, Gomella, L. G., Iozzo, R. V., Baffa, R. |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Male
RNA Messenger/genetics Cell Line Tumor/metabolism/ultrastructure Molecular Sequence Data Neoplasm Proteins/*biosynthesis/genetics Down-Regulation Species Specificity Apoptosis/genetics Urinary Bladder Neoplasms/*genetics/metabolism/pathology Animals Humans Tumor Suppressor Proteins/genetics/isolation & purification/*physiology Chromosomes Human Pair 12/*genetics Cloning Molecular ddc:612 HSP27 Heat-Shock Proteins/biosynthesis/genetics Tumor Stem Cell Assay RNA Neoplasm/genetics Mitochondria/metabolism/ultrastructure Recombinant Fusion Proteins/physiology Cell Transformation Neoplastic/genetics Cell Division/genetics Gene Expression Regulation Neoplastic Genes Tumor Suppressor Disease Progression Female Breast Neoplasms/*genetics/metabolism/pathology |
| Zdroj: | Oncogene, Vol. 28, No 2 (2009) pp. 257-269 |
| ISSN: | 0950-9232 |
| Popis: | Allelic deletions on human chromosome 12q24 are frequently reported in a variety of malignant neoplasms, indicating the presence of a tumor suppressor gene(s) in this chromosomal region. However, no reasonable candidate has been identified so far. In this study, we report the cloning and functional characterization of a novel mitochondrial protein with tumor suppressor activity, henceforth designated MITOSTATIN. Human MITOSTATIN was found within a 3.2-kb transcript, which encoded a approximately 62 kDa, ubiquitously expressed protein with little homology to any known protein. We found homozygous deletions and mutations of MITOSTATIN gene in approximately 5 and approximately 11% of various cancer-derived cells and solid tumors, respectively. When transiently overexpressed, MITOSTATIN inhibited colony formation, tumor cell growth and was proapoptotic, all features shared by established tumor suppressor genes. We discovered a specific link between MITOSTATIN overexpression and downregulation of Hsp27. Conversely, MITOSTATIN knockdown cells showed an increase in cell growth and cell survival rates. Finally, MITOSTATIN expression was significantly reduced in primary bladder and breast tumors, and its reduction was associated with advanced tumor stages. Our findings support the hypothesis that MITOSTATIN has many hallmarks of a classical tumor suppressor in solid tumors and may play an important role in cancer development and progression. |
| Databáze: | OpenAIRE |
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