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题目:: Cyclin D1 depletion induces DNA damage in mantle cell lymphoma lines.
作者:: Mohanty(Suchismita),Mohanty(Atish),Sandoval(Natalie),Tran(Thai),Bedell(Victoria),Wu(Jun),Scuto(Anna),Murata-Collins(Joyce),Weisenburger(Dennis D),Ngo(Vu N)
状态:: 发布时间2016-06-24 , 更新时间 2016-06-24
期刊:: Leuk Lymphoma
摘要:: Elevated cyclin D1 (CCND1) expression levels in mantle cell lymphoma (MCL) are associated with aggressive clinical manifestations related to chemoresistance, but little is known about how this important proto-oncogene contributes to the resistance of MCL. Here, we showed that RNA interference-mediated depletion of CCND1 increased caspase-3 activities and induced apoptosis in the human MCL lines UPN-1 and JEKO-1. In vitro and xenotransplant studies revealed that the toxic effect of CCND1 depletion in MCL cells was likely due to increase in histone H2AX phosphorylation, a DNA damage marker. DNA fiber analysis suggested deregulated replication initiation after CCND1 depletion as a potential cause of DNA damage. Finally, in contrast to depletion or inhibition of cyclin-dependent kinase 4, CCND1 depletion increased chemosensitivity of MCL cells to replication inhibitors hydroxyurea and cytarabine. Our findings have an important implication for CCND1 as a potential therapeutic target in MCL patients who are refractory to standard chemotherapy.
语言:: eng
DOI:: 10.1080/10428194.2016.1198958

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