TAILIEUCHUNG - Báo cáo y học: "Induction of HSPA4 and HSPA14 by NBS1 overexpression contributes to NBS1-induced in vitro metastatic and transformation activity"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: Induction of HSPA4 and HSPA14 by NBS1 overexpression contributes to NBS1-induced in vitro metastatic and transformation activity | Wu et al. Journal of Biomedical Science 2011 18 1 http content 18 1 1 NSC The cost of publication in Journal of Biomedical Science Is borne by the National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access Induction of HSPA4 and HSPA14 by NBS1 overexpression contributes to NBS1-induced in vitro metastatic and transformation activity Chung-Yin Wu1t Chih-Ta Lin2 3t Min-Zu Wu2 Kou-Juey Wu2 Abstract Background Nijmegen breakage syndrome NBS is a chromosomal-instability syndrome associated with cancer predisposition radiosensitivity microcephaly and growth retardation. The NBS gene product NBS1 p95 or nibrin is a part of the MRN complex a central player associated with double-strand break DSB repair. We previously demonstrated that NBS1 overexpression contributes to transformation through the activation of PI 3-kinase Akt. NBS1 overexpression also induces epithelial-mesenchymal transition through the Snail MMP2 pathway. Methods RT-PCR Western blot analysis in vitro migration invasion soft agar colony formation and gelatin zymography assays were performed. Results Here we show that heat shock protein family members A4 and A14 were induced by NBS1 overexpression. siRNA mediated knockdown of HSPA4 or HSPA14 decreased the in vitro migration invasion and transformation activity in H1299 cells overexpressing NBS1. However HSPA4 or HSPA14 induced activity was not mediated through MMP2. NBS1 overexpression induced the expression of heat shock transcription factor 4b HSF4b which correlated with the expression of HSPA4 and HSPA14. Conclusion These results identify a novel pathway NBS1-HSF4b-HSPA4 HSPA14 axis to induce migration invasion and transformation suggesting the activation of multiple signaling events induced by NBS1 overexpression. Introduction Nijmegen breakage syndrome NBS is a chromosomal-instability syndrome associated with cancer predisposition radiosensitivity microcephaly and growth retardation 1-3 . The NBS gene product

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