A NOVEL ROLE OF THE UBCH8-MEDIATED ISGYLATION IN THE ETIOLOGY OF BREAST CANCER
Document Type
Presentation
Start Date
22-10-2010 10:45 AM
End Date
22-10-2010 12:00 PM
Description
ISG15 (Interferon-Stimulated Gene 15) is a 15 kDa protein which is induced by Type I interferons and is a member of the UBL (Ubiquitin-Like Protein) superfamily of proteins. The ISG15 pathway is highly elevated in various human malignancies including breast cancer but not in their normal counterparts, suggesting a role in the etiology of breast cancer. ISG15 exists in both free and target-conjugated forms in tumor cells, however it is not known if either form contributes to breast tumorigenesis. To specifically examine the role of ISG15 conjugates in breast tumorigenesis, we have generated ZR-75-1 and MDA-MB-231 breast cancer cell lines stably expressing UbcHS (ISG15-specific conjugating enzyme) and control shRNA Using these stable transfectants, we demonstrate for the first time that ISG15 conjugates do contribute to breast cell transformation and promotes tumor cell migration. This conclusion is based on two major pieces of evidence: First, both ZR-7.5-1 and MDA-MB-231 breast cancer cells expressing UbcHS shRNA showed reversion of the transformed phenotypes; the UbcHS stable transfectants showed reduced foci formation and colony growth in soft agar, and increased serum dependence. Second, the stable UbcHS shRNA transfectants showed decreased cell migration using wound healing assay. Since the UbcHS sh RNA significantly reduced the amount of ISG15-protein conjugates without affecting the expression level of free ISG15 in both ZR-75-1 and MDA-MB-231 breast cancer cells, our results indicate a role of the ISG15 conjugates (ISGylation), but not free ISG15, in breast tumorigenesis and tumor cell migration. These findings suggest that down-regulation of the ISG15 pathway could be a novel therapeutic approach for the treatment of breast cancers overexpressing ISG15.
Recommended Citation
Burks, Julian and Desai, S. D., "A NOVEL ROLE OF THE UBCH8-MEDIATED ISGYLATION IN THE ETIOLOGY OF BREAST CANCER" (2010). Dr. Joseph M. Moerschbaecher, III Graduate Research Day. 5.
https://digitalscholar.lsuhsc.edu/grad_rs/2010/poster1/5
A NOVEL ROLE OF THE UBCH8-MEDIATED ISGYLATION IN THE ETIOLOGY OF BREAST CANCER
ISG15 (Interferon-Stimulated Gene 15) is a 15 kDa protein which is induced by Type I interferons and is a member of the UBL (Ubiquitin-Like Protein) superfamily of proteins. The ISG15 pathway is highly elevated in various human malignancies including breast cancer but not in their normal counterparts, suggesting a role in the etiology of breast cancer. ISG15 exists in both free and target-conjugated forms in tumor cells, however it is not known if either form contributes to breast tumorigenesis. To specifically examine the role of ISG15 conjugates in breast tumorigenesis, we have generated ZR-75-1 and MDA-MB-231 breast cancer cell lines stably expressing UbcHS (ISG15-specific conjugating enzyme) and control shRNA Using these stable transfectants, we demonstrate for the first time that ISG15 conjugates do contribute to breast cell transformation and promotes tumor cell migration. This conclusion is based on two major pieces of evidence: First, both ZR-7.5-1 and MDA-MB-231 breast cancer cells expressing UbcHS shRNA showed reversion of the transformed phenotypes; the UbcHS stable transfectants showed reduced foci formation and colony growth in soft agar, and increased serum dependence. Second, the stable UbcHS shRNA transfectants showed decreased cell migration using wound healing assay. Since the UbcHS sh RNA significantly reduced the amount of ISG15-protein conjugates without affecting the expression level of free ISG15 in both ZR-75-1 and MDA-MB-231 breast cancer cells, our results indicate a role of the ISG15 conjugates (ISGylation), but not free ISG15, in breast tumorigenesis and tumor cell migration. These findings suggest that down-regulation of the ISG15 pathway could be a novel therapeutic approach for the treatment of breast cancers overexpressing ISG15.