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Published on: November 29, 2016
Expression and function of a novel isoform of Sox5 in malignant B cells
Shanique K E Edwards1, Anand Desai2, Yan Liu2
1Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, United States; Graduate Program in Molecular Biosciences, Rutgers University, Piscataway, NJ 08854, United States.
Abstract:
Using a mouse model with the tumor suppressor TRAF3 deleted from B cells, we identified Sox5 as a gene strikingly up-regulated in B lymphomas. Sox5 proteins were not detected in normal or premalignant TRAF3(-/-) B cells even after treatment with B cell stimuli. The Sox5 expressed in TRAF3(-/-) B lymphomas represents a novel isoform of Sox5, and was localized in the nucleus of malignant B cells. Overexpression of Sox5 inhibited cell cycle progression, and up-regulated the protein levels of p27 and β-catenin in human multiple myeloma cells. Together, our findings indicate that Sox5 regulates the proliferation of malignant B cells.
Insights
Sox5 is upregulated in B cell lymphomas lacking the TRAF3 tumor suppressor. This novel Sox5 isoform inhibits cell cycle progression, suggesting it regulates malignant B cell proliferation.
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- Tumor suppressor TRAF3 (TNFR-associated factor 3) plays a role in B cell malignancies.
- Dysregulation of gene expression is a hallmark of cancer development.
Purpose of the Study:
- To investigate the role of Sox5 in B cell lymphomas.
- To understand the function of Sox5 in malignant B cells.
Main Methods:
- Utilized a mouse model with B cell-specific deletion of TRAF3.
- Analyzed gene and protein expression in normal, premalignant, and malignant B cells.
- Investigated the functional impact of Sox5 overexpression in human multiple myeloma cells.
Main Results:
- Sox5 was significantly upregulated in B lymphomas from TRAF3-deficient mice.
- A novel Sox5 isoform was identified in malignant B cells, localized to the nucleus.
- Sox5 overexpression inhibited cell cycle progression and increased p27 and beta-catenin levels in human multiple myeloma cells.
Conclusions:
- Sox5 is a key regulator of malignant B cell proliferation.
- The novel Sox5 isoform plays a critical role in B cell lymphomagenesis.
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