Expression analysis of Ubc9, the single small ubiquitin-like modifier (SUMO) E2 conjugating enzyme, in normal and malignant tissues

Moschos, Stergios J.; Jukic, Drazen M.; Athanassiou, Charalambos; Bhargava, Rohit; Dacic, Sanja; Wang, Xiaolei; Kuan, Shih-Fan; Fayewicz, Shelley L.; Galambos, Csaba; Acquafondata, Marie; Dhir, Rajiv; Becker, Dorothea

doi:10.1016/j.humpath.2010.02.007

« Previous Next »Human Pathology
Volume 41, Issue 9 , Pages 1286-1298, September 2010

Expression analysis of Ubc9, the single small ubiquitin-like modifier (SUMO) E2 conjugating enzyme, in normal and malignant tissues

Stergios J. Moschos, MD
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
- Corresponding author.
Drazen M. Jukic, MD, PhD
- Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA
- Department of Dermatology, University of Pittsburgh, Pittsburgh, PA 15213, USA
Charalambos Athanassiou, MSc
- Department of Computational Biology, University of Pittsburgh, Pittsburgh, PA 15213, USA
Rohit Bhargava, MD
- Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA
Sanja Dacic, MD, PhD
- Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA
Xiaolei Wang, PhD
- Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA
Shih-Fan Kuan, MD
- Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA
Shelley L. Fayewicz, BSc
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
Csaba Galambos, MD, PhD
- Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA
Marie Acquafondata, BSc
- Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA
Rajiv Dhir, MD
- Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA
Dorothea Becker, PhD
- Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA

Received 8 January 2010; received in revised form 13 February 2010; accepted 17 February 2010. published online 21 June 2010.

Summary

Unlike ubiquitination, which targets proteins for degradation, sumoylation modulates protein-protein interactions of target proteins. Although there are multiple E2 enzymes required for ubiquitination, there is only one E2-conjugating enzyme for sumoylation, which is Ubc9. In line with increasing evidence that sumoylation plays an important role in tumorigenesis, we recently demonstrated that Ubc9 is expressed at high levels in advanced melanomas and that blocking expression of Ubc9 sensitizes melanomas to the cytotoxic effects of chemotherapeutic drugs. To determine whether and to what extent Ubc9 is expressed in other malignancies and their normal tissue counterparts, we undertook a detailed analysis of colon, lung, prostate, and breast cancer tissue microarrays. The findings, presented here, document that in primary colon and prostate cancer, Ubc9 expression is increased compared with their normal tissue counterparts, whereas in metastatic breast, prostate, and lung cancer, it is decreased in comparison with their corresponding normal and primary adenocarcinoma tissues. We also provide evidence that Ubc9 expression correlates positively with Dukes' stage and negatively with the Gleason score as well as breast cancer grade and that Ubc9 expression is substantially higher in the luminal than in the nonluminal type of breast cancer.

Keywords: Ubc9, Cancer, Tissue microarray, Immunohistochemistry, Immune infiltrate