Role of c-myc in Tamoxifen-Induced Apoptosis in Estrogen-Independent Breast Cancer Cells

Background The antiestrogen tamoxifen (TAM) is effective in the treatment of estrogen receptor (ER)-positive as well as some ER-negative breast cancers. However, the precise mechanism of action of TAM, especially in estrogen-independent cells, remains unclear. Previous work by our laboratory has dem...

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Bibliographic Details
Published in:JNCI : Journal of the National Cancer Institute 1996-03, Vol.88 (5), p.279-284
Main Authors: Kang, Yuan, Cortina, Robert, Perry, Roger R.
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Agents, Hormonal - pharmacology
Apoptosis - drug effects
Base Sequence
Biological and medical sciences
Breast cancer
Breast Neoplasms - chemistry
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Cellular biology
Drugs
Estrogen Antagonists - pharmacology
Female
General aspects
Humans
Medical sciences
Molecular Sequence Data
Oligonucleotides, Antisense - pharmacology
Pharmacology. Drug treatments
Proteins
Proto-Oncogene Proteins c-myc - genetics
Proto-Oncogene Proteins c-myc - physiology
Receptors, Estrogen - analysis
Ribonucleic acid
RNA
RNA, Messenger - analysis
Tamoxifen - pharmacology
Tumor Cells, Cultured
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Summary:Background The antiestrogen tamoxifen (TAM) is effective in the treatment of estrogen receptor (ER)-positive as well as some ER-negative breast cancers. However, the precise mechanism of action of TAM, especially in estrogen-independent cells, remains unclear. Previous work by our laboratory has demonstrated that TAM induces the morphologic and biochemical changes that are characteristic of apoptosis in both ER-positive and ER-negative cells. Purpose We compared the effect of TAM at a clinically achievable concentration on cell growth and apoptosis with the effect of TAM on c-myc (also known as C-MYC) messenger RNA (mRNA) and protein expression in ER-negative MDA-231 cells. Methods MDA-231 cells were treated for up to 72 hours with 1.0 μM TAM alone or in the presence of 50 μM c-myc antisense or nonsense oligonucleotides. c-myc mRNA expression was determined by northern blot analysis, protein expression by western blot analysis, cell growth inhibition by cell counts, and DNA cleavage by agarose gel electrophoretic analysis. Differences between the mean values from different treatment groups were compared with the use of the two-sided Wilcoxon rank-sum test. Results: TAM treatment for 72 hours increased c-myc mRNA five-fold (from a relative radiolabeled hybridization signal intensity of 17 ± 4 up to 93 ± 10; P
ISSN:0027-8874
1460-2105
DOI:10.1093/jnci/88.5.279