title: 53BP1 sensitizes breast cancer cells to 5-fluorouracil.
abstract: Chemoresistance of breast cancer is a worldwide problem for breast cancer and the resistance to chemotherapeutic agents frequently led to the subsequent recurrence and metastasis. In our previous study, we have found that 53BP1 showed a gradual decrease during the progression of breast cancer and loss of 53BP1 was associated with metastasis and poor prognosis in breast cancer. Here we aimed to reveal whether 53BP1 could sensitize breast cancer to 5-Fu. We found that ectopic expression of 53BP1 can significantly sensitize breast cancer cells to 5-Fu while knockdown of 53BP1 conferred the resistance. The in vivo experiments confirmed that overexpression of 53BP1 in combination with 5-Fu markedly inhibited growth of xenotransplanted tumors in nude mice when compared to either agent alone. Furthermore, we demonstrated that 53BP1 regulated the sensitivity to 5-Fu through thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPYD). The present studies provide a new clue that combination of 5-Fu and 53BP1 could be a potential novel targeted strategy for overcoming breast cancer chemoresistance.
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Kong
authors.forename: Xiangnan
authors.initials: X
authors.lastname: Kong
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Shi
authors.initials: S
authors.lastname: Yan
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002470:Cell Survival; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D011379:Prognosis; D013940:Thymidylate Synthase / Q000378:metabolism; D000071857:Tumor Suppressor p53-Binding Protein 1; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D047908:Intracellular Signaling Peptides and Proteins; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D005472:Fluorouracil
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