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Lookup NU author(s): Dr Ian HardcastleORCiD
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Tamoxifen, a synthetic antiestrogen, is known for its antitumoral action in vivo; however, it is well accepted that many tamoxifen effects are elicited via estrogen receptor-independent routes. Previously, we reported that tamoxifen induces PKC translocation in fibroblasts. In the present study, we investigated the influence of tamoxifen, and several triphenylethylene derivatives, on protein kinase C (PKC) in MCF-7 human breast cancer cells. As measured by Western blot analysis, tamoxifen elicited isozyme-specific membrane association of PKC-, which was time-dependent (as early as 5 min post-treatment) and dose-dependent (5.0-20 M). Tamoxifen did not influence translocation of , , , or PKC isoforms. Structure-activity relationship studies demonstrated chemical requirements for PKC- translocation, with tamoxifen, 3-OH-tamoxifen and clomiphene being active. Compounds without the basic amino side chain, such as triphenylethylene, or minus a phenyl group, such as N,N-dimethyl-2-[(4-phenylmethyl)phenoxy]ethanamine, were not active. In vitro cell growth assays showed a correlation between agent-induced PKC- translocation and inhibition of cell growth. Exposure of cells to clomiphene resulted in apoptosis. Since PKC- has been associated with cell differentiation and cellular growth-related processes, the antiproliferative influence of tamoxifen on MCF-7 cells may be related to the interaction with PKC-.
Author(s): Lavie Y, Zhang Z, Cao H, Han T-Y, Jones RC, Liu Y-Y, Jarman M, Hardcastle IR, Giuliano AE, Cabot MC
Publication type: Article
Publication status: Published
Journal: International Journal of Cancer
Year: 1998
Volume: 77
Issue: 6
Pages: 928-932
Print publication date: 06/01/1999
ISSN (print): 0020-7136
ISSN (electronic): 1097-0215
Publisher: John Wiley & Sons, Inc.
URL: http://dx.doi.org/10.1002/(SICI)1097-0215(19980911)77:6<928::AID-IJC22>3.0.CO;2-W
DOI: 10.1002/(SICI)1097-0215(19980911)77:6<928::AID-IJC22>3.0.CO;2-W
Notes: Funded by: Breast Cancer Research Program of the University of California; Grant Number: 0211 Ben B. and Joyce E. Eisenberg Foundation, Fashion Footwear Association of New York (FFANY) Shoes on Sale® Cancer Research Campaign, United Kingdom
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