PT  - JOURNAL ARTICLE
AU  - Chauhan, Dharminder
AU  - Li, Guilan
AU  - Shringarpure, Reshma
AU  - Podar, Klaus
AU  - Ohtake, Yasuyuki
AU  - Hideshima, Teru
AU  - Anderson, Kenneth C.
TI  - Blockade of Hsp27 Overcomes Bortezomib/Proteasome Inhibitor PS-341 Resistance in Lymphoma Cells
DP  - 2003 Oct 01
TA  - Cancer Research
PG  - 6174--6177
VI  - 63
IP  - 19
4099  - http://cancerres.aacrjournals.org/content/63/19/6174.short
4100  - http://cancerres.aacrjournals.org/content/63/19/6174.full
SO  - Cancer Res2003 Oct 01; 63
AB  - Bortezomib (PS-341), a selective inhibitor of proteasome, induces apoptosis in various tumor cells, but its mechanism of action is unclear. Treatment with PS-341 induces apoptosis in SUDHL6 (DHL6), but not SUDHL4 (DHL4), lymphoma cells. Microarray analysis shows high RNA levels of heat shock protein-27 (Hsp27) in DHL4 versus DHL6 cells, which correlates with Hsp27 protein expression. Blocking Hsp27 using an antisense strategy restores the apoptotic response to PS-341 in DHL4 cells; conversely, ectopic expression of wild-type Hsp27 renders PS-341-sensitive DHL6 cells resistant to PS-341. These findings provide the first evidence that Hsp27 confers PS-341 resistance. ©2003 American Association for Cancer Research.