skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Synergistic effects of retinoic acid and tamoxifen on human breast cancer cells: Proteomic characterization

Abstract

The anti-estrogen tamoxifen and vitamin A-related compound, all-trans retinoic acid (RA), in combination act synergistically to inhibit the growth of MCF-7 human breast cancer cells. In the present study, we applied two-dimensional gel electrophoresis based proteomic approach to globally analyze this synergistic effect of RA and tamoxifen. Proteomic study revealed that multiple clusters of proteins were involved in RA and tamoxifen-induced apoptosis in MCF-7 breast cancer cells, including post-transcriptional and splicing factors, proteins related to cellular proliferation or differentiation, and proteins related to energy production and internal degradation systems. The negative growth factor-transforming growth factor {beta} (TGF{beta}) was secreted by RA and/or tamoxifen treatment and was studies as a potential mediator of the synergistic effects of RA and tamoxifen in apoptosis. By comparing protein alterations in treatments of RA and tamoxifen alone or in combination to those of TGF{beta} treatment, or co-treatment with TGF{beta} inhibitor SB 431542, proteomic results showed that a number of proteins were involved in TGF{beta} signaling pathway. These results provide valuable insights into the mechanisms of RA and tamoxifen-induced TGF{beta} signaling pathway in breast cancer cells.

Authors:
 [1];  [1];  [2];  [3]
  1. Department of Chemistry, University of Hong Kong, Pokfulam, Hong Kong (China)
  2. Department of Biochemistry, University of Vermont, College of Medicine, Burlington 05405 (United States)
  3. Department of Anatomy, The University of Hong Kong, Pokfulam, Hong Kong (China) and Department of Biochemistry, University of Vermont, College of Medicine, Burlington 05405 (United States). E-mail: jfchiu@hkucc.hku.hk
Publication Date:
OSTI Identifier:
20972107
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 313; Journal Issue: 2; Other Information: DOI: 10.1016/j.yexcr.2006.10.016; PII: S0014-4827(06)00442-3; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; BROMIDES; CELL PROLIFERATION; ELECTROPHORESIS; ESTROGENS; GELS; GROWTH FACTORS; HEAT-SHOCK PROTEINS; IODIDES; MAMMARY GLANDS; NEOPLASMS; RECEPTORS; RETINOIC ACID; TAMOXIFEN; VITAMIN A

Citation Formats

Wang Ying, He Qingyu, Chen Hongming, and Chiu Jenfu. Synergistic effects of retinoic acid and tamoxifen on human breast cancer cells: Proteomic characterization. United States: N. p., 2007. Web. doi:10.1016/j.yexcr.2006.10.016.
Wang Ying, He Qingyu, Chen Hongming, & Chiu Jenfu. Synergistic effects of retinoic acid and tamoxifen on human breast cancer cells: Proteomic characterization. United States. doi:10.1016/j.yexcr.2006.10.016.
Wang Ying, He Qingyu, Chen Hongming, and Chiu Jenfu. 2007. "Synergistic effects of retinoic acid and tamoxifen on human breast cancer cells: Proteomic characterization". United States. doi:10.1016/j.yexcr.2006.10.016.
@article{osti_20972107,
title = {Synergistic effects of retinoic acid and tamoxifen on human breast cancer cells: Proteomic characterization},
author = {Wang Ying and He Qingyu and Chen Hongming and Chiu Jenfu},
abstractNote = {The anti-estrogen tamoxifen and vitamin A-related compound, all-trans retinoic acid (RA), in combination act synergistically to inhibit the growth of MCF-7 human breast cancer cells. In the present study, we applied two-dimensional gel electrophoresis based proteomic approach to globally analyze this synergistic effect of RA and tamoxifen. Proteomic study revealed that multiple clusters of proteins were involved in RA and tamoxifen-induced apoptosis in MCF-7 breast cancer cells, including post-transcriptional and splicing factors, proteins related to cellular proliferation or differentiation, and proteins related to energy production and internal degradation systems. The negative growth factor-transforming growth factor {beta} (TGF{beta}) was secreted by RA and/or tamoxifen treatment and was studies as a potential mediator of the synergistic effects of RA and tamoxifen in apoptosis. By comparing protein alterations in treatments of RA and tamoxifen alone or in combination to those of TGF{beta} treatment, or co-treatment with TGF{beta} inhibitor SB 431542, proteomic results showed that a number of proteins were involved in TGF{beta} signaling pathway. These results provide valuable insights into the mechanisms of RA and tamoxifen-induced TGF{beta} signaling pathway in breast cancer cells.},
doi = {10.1016/j.yexcr.2006.10.016},
journal = {Experimental Cell Research},
number = 2,
volume = 313,
place = {United States},
year = 2007,
month = 1
}
  • Carcinogen-DNA adducts could lead to mutations in critical genes, eventually resulting in cancer. Many studies have shown that retinoic acid (RA) plays an important role in inducing cell apoptosis. Here we have tested the hypothesis that levels of carcinogen-DNA adducts can be diminished by DNA repair and/or by eliminating damaged cells through apoptosis. Our results showed that the levels of total DNA adducts in HepG2 cells treated with benzo(a)pyrene (BP, 2 {mu}M) + RA (1 {mu}M) were significantly reduced compared to those treated with BP only (P = 0.038). In order to understand the mechanism of attenuation of DNA adducts,more » further experiments were performed. Cells were treated with BP (4 {mu}M) for 24 h to initiate DNA adduct formation, following which the medium containing BP was removed, and fresh medium containing 1 {mu}M RA was added. The cells were harvested 24 h after RA treatment. Interestingly, the levels of total DNA adducts were lower in the BP/RA group (390 {+-} 34) than those in the BP/DMSO group (544 {+-} 33), P = 0.032. Analysis of cell apoptosis showed an increase in BP + RA group, compared to BP or RA only groups. Our results also indicated that attenuation of BP-DNA adducts by RA was not primarily due to its effects on CYP1A1 expression. In conclusion, our results suggest a mechanistic link between cellular apoptosis and DNA adduct formation, phenomena that play important roles in BP-mediated carcinogenesis. Furthermore, these results help understand the mechanisms of carcinogenesis, especially in relation to the chemopreventive properties of nutritional apoptosis inducers.« less
  • In the present study, we have examined the neutral glycolipids, gangliosides, and sulfoglycolipids of human rectal adenocarcinoma (HRT-18) cells and the alterations produced by the differentiating agents, sodium butyrate, dimethyl sulfoxide, and retinoic acid. Thin-layer chromatography of neutral glycolipids showed that HRT-18 cells contained mono- and diglycosylceramides. Cells treated with differentiating agents had additional glycolipids which comigrated with tri- and tetraglycosylceramides. Labeling of neutral glycolipids with (/sup 3/H)galactose showed that HRT-18 cells also contain glycosylceramides larger than diglycosylceramides which also were altered by treatment with differentiating agents. In studies of acidic glycolipids, GM3, the major ganglioside in untreated cells, wasmore » reduced in cells treated with retinoic acid but not in cells treated with other agents. Upon labeling with radioactive galactose, changes were seen only in the minor ganglioside components of treated cells. Differentiating agents also altered the patterns of sulfogalactolipids and fucolipids in HRT-18 cells. In the case of fucolipids, 2 new bands were observed in the cells treated with dimethyl sulfoxide and retinoic acid. The changes brought about by differentiating agents may identify glycolipids involved in the process of tumorigenicity.« less
  • The incidence of breast cancer in western societies has been rising ever since the Second World War. Besides the exposure to a multitude of new chemical compounds, electromagnetic field exposure has been linked to breast cancer through a radiation-mediated anti-melatonin pathway. We investigated, whether low-frequency electromagnetic field exposure interferes with the anti-estrogenic activity of tamoxifen. Two different clones of the breast cancer cell line MCF-7 were exposed to highly homogeneous 50 Hz electromagnetic fields and IC{sub 50} values were calculated from dose-response curves of tamoxifen at various field intensities. An intensity-dependent shift of tamoxifen dose-response curves to higher concentrations withmore » a maximal response at 1.2 {mu}T was observed. Hypothetically, electromagnetic field exposure could contribute to tamoxifen resistance observed in breast cancer after long-term treatment.« less
  • Acquired resistance to tamoxifen has become a serious obstacle in breast cancer treatment. The underlying mechanism responsible for this condition has not been completely elucidated. In this study, a tamoxifen-resistant (Tam-R) MCF-7 breast cancer cell line was developed to mimic the occurrence of acquired tamoxifen resistance as seen in clinical practice. Increased expression levels of HER1, HER2 and the estrogen receptor (ER)-AIB1 complex were found in tamoxifen-resistant cells. EGF stimulation and gefitinib inhibition experiments further demonstrated that HER1/HER2 signaling and AIB1 were involved in the proliferation of cells that had acquired Tam resistance. However, when AIB1 was silenced with AIB1-siRNAmore » in Tam-R cells, the cell growth stimulated by the HER1/HER2 signaling pathway was significantly reduced, and the cells were again found to be inhibited by tamoxifen. These results suggest that the AIB1 protein could be a limiting factor in the HER1/HER2-mediated hormone-independent growth of Tam-R cells. Thus, AIB1 may be a new therapeutic target, and the removal of AIB1 may decrease the crosstalk between ER and the HER1/HER2 pathway, resulting in the restoration of tamoxifen sensitivity in tamoxifen-resistant cells.« less