Posted May 21, 2013
Michael Burns, B.S., University of Minnesota, Twin Cities, Minneapolis, Minnesota,
Fiscal Year 2010 Predoctoral Traineeship Award
Reuben Harris, Ph.D., University of Minnesota, Twin Cities, Minneapolis, Minnesota, Mentor
It is largely accepted that gene mutations are generally harmful and can lead to the development and progression of breast cancer; however, the underlying mechanism for how these mutations contribute to cancer is still unclear. Michael Burns, a Fiscal Year 2010 Breast Cancer Research Program (BCRP) Predoctoral Traineeship Award recipient, is working under the mentorship of Dr. Reuben Harris at the University of Minnesota (Twin Cities campus) to understand the role of these mutations and establish the molecular underpinnings of breast cancer development.
Mr. Burns, Dr. Harris, and colleagues recently revealed a role for the DNA-mutating enzyme APOBEC3B in breast cancer. They found APOBEC3B overexpressed in two-thirds of breast cancer cell lines and over half of all tumors examined. In contrast, APOBEC3B was detected at low levels in normal breast tissues and mammary epithelial cell lines. Additional cell culture studies performed by Dr. Harris' group showed an increase in C-to-T DNA mutations in cell lines where APOBEC3B was upregulated. This finding is significant as C-to-T mutations are the most common type of mutation found in breast cancer. Genetic selection assays further demonstrated that increased expression of APOBEC3B in breast cancer cell lines enabled the cells to escape toxic drug treatment. The upregulation of APOBEC3B also correlated with mutation load, and the APOBEC3B mutation signature was found all over the breast cancer genome. The results of this BCRP-funded research on APOBEC3B and its role in breast cancer were recently published in the journal Nature.
These findings have yielded valuable clues toward understanding and treating breast cancer. Inhibition of APOBEC3B may be beneficial in providing more stable targets for current breast cancer therapeutics. Characterizing the mechanism that drives APOBEC3B expression may help researchers determine targetable pathways in which the mutational capacity of APOBEC3B in breast cancer can be decreased, and the efficacy of therapeutics used to treat the disease may be improved. Mr. Burns and Dr. Harris express that their next step toward bringing their research to help breast cancer patients is to "aim to collaborate to determine how APOBEC3B influences long-term survival and drug resistance."
Burns MB, Lackey L, Carpenter MA, Rathore A, Land AM, Leonard B, Refsland EW, Kotandeniya D, Tretyakova N, Nikas JB, Yee D, Temiz NA, Donohue DE, McDougle RM, Brown WL, Law EK, and Harris RS. 2013. APOBEC3B is an enzymatic source of mutation in breast cancer. Nature 494(7437):366-370.
Public and Technical Abstracts: Mutation of Breast Cancer Cell Genomic DNA by APOBEC3B