Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exposure of cells to bortezomib (BTZ) could activate heat shock protein (HSP) expression, which is regulated mainly by heat shock factor 1 (HSF1). We determined the role of Apg-1 (HSPA4L, a member of the HSP110 family) in HSF1 activation and bortezomib sensitivity by silencing HSF1 in multiple myeloma (MM) cells. We observed that the Apg-1 protein level was upregulated as BTZ concentration increased. To investigate the mechanism underlying Apg-1 induction, we evaluated the HSF1 translocation and found BTZ-inducible transposition to the nucleus of HSF1. In addition, cleaved caspase 3 and PARP might account for increased BTZ sensitivity on Apg-1 silencing. Furthermore, silencing HSF1 with shRNA or triptolide resulted in significant BTZ sensitivity. It had a more profound effect on cell death caused by BTZ when myeloma cells were adherent to bone marrow stromal cell lines (Hs-5). In summary, we found that Apg-1 knockdown sensitized myeloma cells to bortezomib treatment, which may provide a new approach in multiple myeloma treatment.
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PMID:Role of Apg-1 in HSF1 activation and bortezomib sensitivity in myeloma cells. 3189 17