Diacylglycerol Signaling

23 Atypical PKCs as Targets for Cancer Therapy
Table 23.1 Summary of atypical PKC function in human cancer. Although the aPKCs (PKCz and PKCi/l ) share high sequence homology, they possess
distinct and often dramatic functional differences in both normal and tumor tissues. In the majority of transformed systems evaluated to date, PKCz exhibits
either tumor-suppressor activity, or little to no discernible role in tumorigenesis. PKCi, in contrast, plays a critical promotive role in transformed growth,
invasion, migration, survival, chemoresistance, and tumor proliferation in numerous tumor model systems in vitro and in vivo. In addition, PKCi is the first
and only PKC isozyme to be identified as an oncogene in human cancer
In vitro and in vivo animal
models
May act as tumor
suppressor (Galvez
et al. 2009)
May act as tumor
suppressor; inhibits
transformed growth of
colon cells in vitro and
colon tumor formation
in vivo (Mustafi
et al. 2006; Oster and
Leitges 2006)
PKCi/l PKCz
In vitro and in vivo animal
Tumor type Primary tumors
models Primary tumors
Nonsmall cell lung cancer Overexpressed, amplified, Overexpressed and
Low levels of expression
oncogene, prognostic amplified in NSCLC in normal and tumor
indicator (Regala et al. cell lines; promotes tissues; no change in
2005a; b)
chemoresistance
expression between
transformed
normal and tumor
growth, invasion,
tissues
migration and tumor
proliferation (Regala
et al. 2005a; b;
Frederick et al. 2008)
Leukemia Overexpressed (Gustafson
et al. 2004), mediates
chemoresistance
(Jamieson et al. 1999;
Lu et al. 2001; Murray
et al. 1999)
Colon cancer Increased expression in Overexpressed and promotes
human colon carcinoma tumor development /
(Murray et al. 2004)
progression in AOM,
APCMin/+ and K-rasLA colon carcinogenesis
models (Murray et al.
2004; Gokmen-Polar
et al. 2001; Murray et al.
2009)
459
(continued)