Abstract LB-189: Fbxo7 functions in the proliferation and maturation of hematopoietic cells
| Autor: | El Kahina Meziane, Suzanne J. Randle, Heike Laman, Mikhail Lomonosov |
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| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | Cancer Research. 71:LB-189 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2011-lb-189 |
| Popis: | The F-box protein Fbxo7 specifically enhances the levels of cyclin D-Cdk6 complexes, the predominant G1 kinase active in hematopoietic cells, which is a commonly activated oncogenic pathway in lymphoid neoplasms. In addition, Fbxo7 is itself abundantly expressed in high-grade B and T cell malignancies. Previously we have tested the ability of Fbxo7 to act as an oncogene in the hematopoietic compartment in adoptive transfer experiments using p53 null hematopoietic stem cells over expressing Fbxo7. Animals reconstituted with these cells develop T cell lymphoma, supporting the idea that Fbxo7 can have tumor promoting activity in vivo. However, in experiments presented here, to investigate the transforming capacity of Fbxo7 in B lymphocytes, we found that overexpression of Fbxo7 in the mouse pro-B cell line Ba/F3 did not transform cells nor enhance their proliferation. Instead, the stable reduction of Fbxo7 expression increased proliferation and decreased cell size, which were attributable to shortening of G1 phase, decreased p27 levels and increased Cdk2 activity. These results suggest that Fbxo7 normally restrains proliferation in pro-B cells. Reducing Fbxo7 expression also changed the cell surface marker phenotype to resemble a more immature state of B cell maturation. To investigate the activities of Fbxo7 in hematopoietic cells in a more physiological setting, we have generated an in vivo model of reduced Fbxo7 expression by engineering a mouse with an insertional mutation of the LacZ gene into the FBXO7 locus. Phenotypic characterization of these mice will also be presented, and these data support the idea that Fbxo7 regulates the proliferation and the maturation of different precursor cell populations, including pro-B cells and pro-erythroblasts. We propose that Fbxo7 has the capacity to function as a tumor suppressor and also as an oncogene depending on the cell type and its stage of differentiation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-189. doi:10.1158/1538-7445.AM2011-LB-189 |
| Databáze: | OpenAIRE |
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