Tumorigenic properties of iron regulatory protein 2 (IRP2) mediated by its specific 73-amino acids insert
| Autor: | Christos C. Ouzounis, Kostas Pantopoulos, Ignat Drozdov, Guohua Chen, Carmen Maffettone |
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| Rok vydání: | 2009 |
| Předmět: |
Lung Neoplasms
Transgene Transplantation Heterologous Cell Biology/Cell Growth and Division lcsh:Medicine Mice Nude Transferrin receptor Mice Transgenic Computational Biology/Comparative Sequence Analysis Biology Cell Biology/Cell Signaling Mice Cell Line Tumor Molecular Biology/Translational Regulation Gene expression Animals Humans lcsh:Science Iron Regulatory Protein 2 Molecular Biology Cell Biology/Gene Expression Sequence Deletion chemistry.chemical_classification Regulation of gene expression Multidisciplinary Microarray analysis techniques Gene Expression Profiling lcsh:R Wild type Molecular biology Amino acid Gene expression profiling Gene Expression Regulation Neoplastic chemistry Oncology lcsh:Q Hematology/Anemias Molecular Biology/RNA-Protein Interactions Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 5, Iss 4, p e10163 (2010) |
| ISSN: | 1932-6203 |
| Popis: | Iron regulatory proteins, IRP1 and IRP2, bind to mRNAs harboring iron responsive elements and control their expression. IRPs may also perform additional functions. Thus, IRP1 exhibited apparent tumor suppressor properties in a tumor xenograft model. Here we examined the effects of IRP2 in a similar setting. Human H1299 lung cancer cells or clones engineered for tetracycline-inducible expression of wild type IRP2, or the deletion mutant IRP2(Delta73) (lacking a specific insert of 73 amino acids), were injected subcutaneously into nude mice. The induction of IRP2 profoundly stimulated the growth of tumor xenografts, and this response was blunted by addition of tetracycline in the drinking water of the animals, to turnoff the IRP2 transgene. Interestingly, IRP2(Delta73) failed to promote tumor growth above control levels. As expected, xenografts expressing the IRP2 transgene exhibited high levels of transferrin receptor 1 (TfR1); however, the expression of other known IRP targets was not affected. Moreover, these xenografts manifested increased c-MYC levels and ERK1/2 phosphorylation. A microarray analysis identified distinct gene expression patterns between control and tumors containing IRP2 or IRP1 transgenes. By contrast, gene expression profiles of control and IRP2(Delta73)-related tumors were more similar, consistently with their growth phenotype. Collectively, these data demonstrate an apparent pro-oncogenic activity of IRP2 that depends on its specific 73 amino acids insert, and provide further evidence for a link between IRPs and cancer biology. |
| Databáze: | OpenAIRE |
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