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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 09, 2007 |
| Title |
The Differentiation and Stress Response Factor, XBP-1, Drives Multiple Myeloma Pathogenesis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Multiple myeloma (MM) evolves from highly prevalent premalignant condition termed Monoclonal Gammopathy of Undetermined Significance (MGUS). We report an MGUS-MM phenotype arising in transgenic mice with Emu-directed expression of the unfolded protein/ER stress response and plasma cell development spliced isoform factor XBP-1s. Emu-XBP-1s elicited elevated serum Ig and IL-6 levels, skin alterations and with advancing age, a significant proportion of Emu-xbp-1s transgenic mice develop features diagnostic of human MM including bone lytic lesions. Transcriptional profiles of Emu-xbp-1s B lymphoid and MM cells show aberrant expression of genes known to be dysregulated in human MM including Cyclin D1, MAF, MAFB, and APRIL. This genetic model coupled with documented frequent XBP-1s overexpression in human MM serve to implicate chronic XBP-1s dysregulation in the development of this common and lethal malignancy.
Keywords: XBP-1, MGUS, multiple myeloma, transgenic mouse
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| Overall design |
In this study, we have explored the biological impact of sustained XBP-1s expression in the lymphoid system, anticipating that this genetic event would be a necessary component along with other MM-relevant oncogenes and tumor suppressor gene manipulations to generate a MM-prone mouse model. Unexpectedly, XBP-1s overexpression alone yielded an MGUS-MM disease bearing many features classical of the human disease on the clinical, pathological and molecular levels.
We performed expression analysis of B cells derived from the spleen of 20-week old Emu-xbp-1s mice (n=5) and non-transgenic mice (n=5). Additionally, we analyzed the expression profiles from MM tumor cells arising in Emu-xbp-1s mice (n=6).
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| Contributor(s) |
Carrasco DR, Sukhdeo K, Protopopova M, Sinha R, Enos M, Carrasco DE, Zheng M, Mani M, Henderson J, Pinkus GS, Munshi N, Horner J, Ivanova EV, Protopopov A, Anderson KC, Tonon G, DePinho RA |
| Citation(s) |
17418411 |
| Submission date |
Feb 07, 2007 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Ronald A DePinho |
| E-mail(s) |
ron_depinho@dfci.harvard.edu, giovanni_tonon@dfci.harvard.edu, ruben_carrasco@dfci.harvard.edu
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| Organization name |
Dana Farber Cancer Institute
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| Street address |
44 Binney St. M417
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA99289 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE6980_RAW.tar |
68.6 Mb |
(http)(custom) |
TAR (of CEL) |
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