Notch versus the proteasome: what is the target of γ-secretase inhibitor-I?
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* Corresponding author: Clodia Osipo cosipo@lumc.edu
1 Molecular and Cellular Biochemistry Program, The Stritch School of Medicine at Loyola University Medical Center, Loyola University Chicago, 2160 S. First Avenue, Maywood, IL 60153, USA
2 Department of Pathology, Oncology Institute, The Stritch School of Medicine at Loyola University Medical Center, Loyola University Chicago, 2160 S. First Avenue, Maywood, IL 60153, USA
3 Molecular Biology Program, The Stritch School of Medicine at Loyola University Medical Center, Loyola University Chicago, 2160 S. First Avenue, Maywood, IL 60153, USA
Breast Cancer Research 2009, 11:110 doi:10.1186/bcr2407
Published: 15 October 2009Abstract
γ-Secretase inhibitors are new anti-cancer agents targeting Notch signaling. Their specificity for Notch is as yet unclear. Han and colleagues investigated the effects of Z-LeuLeuNleu-CHO on growth of breast cancer cells. The results demonstrated a reduction in cell viability primarily via proteasome inhibition independent of Notch activity. Currently, γ-secretase inhibitors in clinical trials are structurally distinct from Z-LeuLeuNleu-CHO. Their effects on the proteasome are yet to be determined. However, findings from Han and colleagues pose two critical questions: Is the level of proteasomal activity in breast tumors the driving force for growth? What does the Notch pathway contribute to this growth?