Diacylglycerol Signaling

Chapter 17
PKC and Breast Cancer *
Sofia D. Merajver, Devin T. Rosenthal, and Lauren Van Wassenhove
Abstract PKC expression is intimately associated with breast cancer initiation,
progression, and therapy responsiveness, and these effects are highly isozymespecific.
PKC isozymes play key roles in proliferation and apoptosis of breast
cancer cells and exert important modulatory roles in cell cycle progression. A close
relationship exists between specific PKC isozymes and estrogen signaling.
Keywords Protein kinase C • Breast cancer progression • Estrogen receptor
signaling • Drug resistance
17.1 Introduction
As discussed earlier in this book, PKC is an important component of numerous key
cell signaling pathways: it serves as a crucial hub for translating a variety of extracellular
stimuli into cellular responses. In this chapter, we illustrate the role of PKC
isozymes in breast cancer development and progression, with a focus on how the tumorigenic
properties of PKC reflect its role in normal mammary gland development.
There are some general attributes shared by most PKC isoforms, yet each isozyme
retains its own identity through distinct roles in breast cancer progression. An enhanced
understanding of the involvement of specific isozymes is essential to the development
of effective targeted therapies with minimal side effects, as is already evidenced
through the early successes of small molecule inhibitors of PKC such as enzastaurin.
* Work supported by NIH RO1CA-61722 (SDM), the Burroughs Wellcome Fund (SDM), the
Department of Defense Breast Cancer Program (predoctoral grant to DTR), the UM Cellular
Biotechnology Training Grant (LVW) and the Breast cancer Research Foundation (SDM).
S.D. Merajver (*), D.T. Rosenthal, and L.V. Wassenhove
Department of Internal Medicine, Division of Hematology and Oncology,
University of Michigan, Ann Arbor, MI, USA
e-mail: smerajve@med.umich.edu
M.G. Kazanietz (ed.), Protein Kinase C in Cancer Signaling and Therapy,
Current Cancer Research, DOI 10.1007/978-1-60761-543-9_17,
© Springer Science+Business Media, LLC 2010
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