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A role for Ubc9 in tumorigenesis
Yin-Yuan Mo1, Yanni Yu, Elena Theodosiou
1Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA. ymo@siumed.edu
Oncogene
|March 1, 2005
Summary
Elevated Ubc9 levels in ovarian tumors suggest a role in cancer. Ubc9 promotes tumor growth by regulating bcl-2 expression, impacting apoptosis and cell survival.
Area of Science:
- Molecular Biology
- Cellular Biology
- Oncology
Background:
- Post-translational modifications like ubiquitination and sumoylation regulate cellular pathways.
- Ubc9 is the essential E2-conjugating enzyme for sumoylation.
- Alterations in ubiquitination pathways are linked to cancer, but the role of sumoylation in tumorigenesis is unclear.
Purpose of the Study:
- To investigate the role of Ubc9 in tumorigenesis.
- To determine if Ubc9 expression levels correlate with ovarian tumor development.
- To elucidate the mechanism by which Ubc9 influences tumor growth.
Main Methods:
- Analysis of Ubc9 expression in ovarian tumors versus normal tissues.
- Overexpression of wild-type Ubc9 (Ubc9-WT) and a dominant-negative mutant (Ubc9-DN) in MCF-7 breast cancer cells.
- Xenograft studies in mice and cell culture experiments to assess tumor growth.
- Microarray analysis to profile gene expression changes.
- Apoptosis assays and survival studies.
Main Results:
- Ubc9 expression was elevated in ovarian tumors.
- Ubc9-WT overexpression enhanced tumor growth, while Ubc9-DN expression reduced it in vitro and in vivo.
- Microarray analysis revealed altered expression of the pro-oncogene bcl-2.
- Ubc9-DN expression led to increased apoptosis and reduced cell survival, correlating with bcl-2 downregulation.
Conclusions:
- Ubc9 expression is elevated in ovarian tumors, suggesting its involvement in tumorigenesis.
- Ubc9 promotes tumor growth, at least partially through the regulation of bcl-2 expression.
- These findings highlight Ubc9 as a potential target in cancer therapy.