Sensitivity of tumor cells to proteasome inhibitors is associated with expression levels and composition of proteasome subunits

Cancer
Antonia BusseUlrich Keilholz

Abstract

Sensitivity of tumor cells to induction of apoptosis by proteasome inhibitors varies greatly. This study was undertaken to investigate the sensitivity of neoplastic B cells and solid tumor cells to proteasome inhibition with respect to constitutive expression levels of proteasome subunits. Twelve neoplastic B-cell lines and 12 solid tumor cell lines were assessed for their expression levels of proteasome subunits by using quantitative reverse transcriptase-polymerase chain reaction analysis and were assessed for their sensitivity to the proteasome inhibitors PS-341 and lactacystin by using a flow cytometry assay that detected activated caspases. The neoplastic B-cell lines were categorized into 3 groups representing refractory cell lines, cell lines with moderate sensitivity, and cell lines with high sensitivity. Correlating expression levels of proteasome subunits with sensitivity to proteasome inhibition indicated that refractory B cells exhibited lower expression levels of the standard subunit beta2 and of the immunoproteasome subunit LMP2 compared with sensitive B cell lines. Compared with neoplastic B cells solid tumor cells were less sensitive. They expressed the immunoproteasome subunits LMP2, LMP7 and MECL-1 and the sta...Continue Reading

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Citations

Mar 23, 2013·Clinical & Experimental Metastasis·Antonia BusseUlrich Keilholz
Jul 14, 2011·Investigational New Drugs·Martin Schmidt-HieberIgor Wolfgang Blau
Mar 2, 2011·Molecular & Cellular Proteomics : MCP·Ding WangPeipei Ping
Feb 10, 2011·Journal of Gastroenterology and Hepatology·Yuan LvChangqing Xu
Jan 5, 2012·PloS One·Erika SuzukiChristopher J Kirk
Jan 3, 2016·Archives of Biochemistry and Biophysics·Burkhardt Dahlmann
Oct 27, 2011·Biochemical Pharmacology·Leonie H A M de WiltFrank A E Kruyt
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Dec 6, 2014·Cancer Chemotherapy and Pharmacology·Jannick ClemensJohanna Weiss
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