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Phospholipase C–protein kinase C mediated phospholipase D activation pathway is involved in tamoxifen induced apoptosis
Author(s) -
Ahn SooJung,
Yoon MeeSup,
Hyuk Shin,
Han Wonshik,
Yoon YongDal,
Han JoongSoo,
Noh DongYoung
Publication year - 2003
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10532
Subject(s) - phospholipase d , protein kinase c , diacylglycerol kinase , phospholipase c , apoptosis , cancer research , signal transduction , phosphoinositide phospholipase c , microbiology and biotechnology , tamoxifen , biology , chemistry , cancer , medicine , biochemistry , breast cancer
Tamoxifen (TAM) is the endocrine therapeutic agent the most widely used in the treatment of breast cancer, and it operates primarily through the induction of apoptosis. In this study, we attempted to elucidate the non‐ER mediated mechanism behind TAM treatment, involving the phospholipase C–protein kinase C (PLC–PKC) mediated phospholipase D (PLD) activation pathway, using multimodality methods. In TAM treated MCF7 cells, the PLC and PLD protein and mRNA levels increased. Phosphatidylethanol (PEt) and diacylglycerol (DAG) generation also increased, showing increased activity of PLD and PLCγ1. Translocation of PKCα, from cytosol to membrane, was observed in TAM treated cells. By showing that both PKC and PLC inhibitors could reduce the effects of TAM‐induced PLD activation, we confirmed the role of PKC and PLC as upstream regulators of PLD. Finally, we demonstrated that TAM treatment reduced the viability of MCF7 cells and brought about rapid cell death. From these results, we confirmed the hypothesis that TAM induces apoptosis in breast cancer cells, and that the signal transduction pathway, involving PLD, PLC, and PKC, constitutes one of the possible mechanisms underlying the non‐ER mediated effects associated with TAM. © 2003 Wiley‐Liss, Inc.