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[Cancer Research 63, 6174-6177, October 1, 2003]
© 2003 American Association for Cancer Research

Advances in Brief

Blockade of Hsp27 Overcomes Bortezomib/Proteasome Inhibitor PS-341 Resistance in Lymphoma Cells1

Dharminder Chauhan, Guilan Li2, Reshma Shringarpure2, Klaus Podar, Yasuyuki Ohtake, Teru Hideshima and Kenneth C. Anderson3

The Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115 [D. C., G. L., R. S., K. P., T. H., K. C. A.], and R & D Planning Department, Asahi Breweries, Ltd., Tokyo, 130-8602, Japan [Y. O.]

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.




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