- 作者: Chung-Yin Wu; Chih-Ta Lin; Min-Zu Wu; Kou-Juey Wu
- 作者服務機構: Department of Occupational Medicine, Far Eastern Memorial Hospital, Taipei County, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
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. - 中文關鍵字: --
- 英文關鍵字: --