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(A3)Beating Cancer: Impact of APOBEC3B on 5‐Fluorouracil Treatment
Author(s) -
Fine Sydney R
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.775.9
Subject(s) - clonogenic assay , thymidylate synthase , cancer research , cancer , biology , cancer cell , fluorouracil , cell , medicine , genetics
The APOBEC3 family of cytosine deaminases consists of seven members that function as part of the innate immunity. One family member, APOBEC3B (A3B), has been implicated as an endogenous source of mutation in cancer cells, specifically in head/neck, lung, cervical and breast cancers. A3B increases the rate of mutation in DNA through its ability to deaminate cytosine into uracil. The aim of this study was to determine if A3B over‐expression synergizes with 5‐Fluorouracil (5‐FU), an FDA‐approved chemotherapeutic agent, to promote cell death. 5‐FU promotes cell death through two mechanisms. First, 5‐FU inhibits thymidylate synthase, an enzyme that converts deoxyuridylate to deoxythymidylate. Second, 5‐FU becomes incorporated into DNA, which causes significant DNA damage. To investigate the hypothesis, A3B was over‐expressed in a mammary epithelial cell line, MCF10A. Then, the cells were treated with various concentrations of 5‐FU. Cell viability in response to 5‐FU treatment was assessed by clonogenic survival assays, which measure cells' ability to proliferate. It was determined that up‐regulation of A3B had little to no effect on the efficacy of 5‐FU. This research has implications in regards to personalized treatment in cancer patients with A3B‐high tumors because treating these tumors with 5‐FU may widen the therapeutic window and allow for more effective disease treatment. Support or Funding Information The Harris lab is supported by grants from the NIH. Dr. Harris is an Investigator of the Howard Hughes Medical Institute. The NIH provides funding for the Cancer Research Education & Training Experience.