Notch versus the proteasome: what is the target of γ-secretase inhibitor-I?

doi:10.1186/bcr2407

Breast Cancer Research

Volume 11
Issue 5

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Editorial

Notch versus the proteasome: what is the target of γ-secretase inhibitor-I?

Anthony G Clementz¹ and Clodia Osipo¹^,2^,3

¹Molecular 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

²Department 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

³Molecular Biology Program, The Stritch School of Medicine at Loyola University Medical Center, Loyola University Chicago, 2160 S. First Avenue, Maywood, IL 60153, USA

author email corresponding author email

Breast Cancer Research 2009, 11:110doi:10.1186/bcr2407


Published:	15 October 2009

See related research by Han et al., http://breast-cancer-research.com/content/11/4/R57

Abstract

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?