The Differentiation and Stress Response Factor XBP-1 Drives Multiple Myeloma Pathogenesis
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- 作者：Daniel R. Carrasco ; Kumar Sukhdeo ; Marina Protopopova ; Raktim Sinha ; Miriam Enos ; Daniel ; E. Carrasco ; Mei Zheng ; Mala Mani ; Joel Henderson ; Geraldine S. Pinkus ; Nikhil Munshi ; James Horner ; Elena
- 关键词：CELLCYCLE
- 刊名：Cancer Cell
- 出版年：2007
- 出版时间：10 April 2007
- 年：2007
- 卷：11
- 期：4
- 页码：349-360
- 全文大小：1603 K
文摘
Multiple myeloma (MM) evolves from a highly prevalent premalignant condition termed MGUS. The factors underlying the malignant transformation of MGUS are unknown. We report a MGUS/MM phenotype in transgenic mice with Eμ-directed expression of the XBP-1 spliced isoform (XBP-1s), a factor governing unfolded protein/ER stress response and plasma-cell development. Eμ-XBP-1s elicited elevated serum Ig and skin alterations. With age, Eμ-xbp-1s transgenics develop features diagnostic of human MM, including bone lytic lesions and subendothelial Ig deposition. Furthermore, transcriptional profiles of Eμ-xbp-1s lymphoid and MM cells show aberrant expression of known human MM dysregulated genes. The similarities of this model with the human disease, coupled with documented frequent XBP-1s overexpression in human MM, serve to implicate XBP-1s dysregulation in MM pathogenesis.