caa a22 4500 397564155 CHVBK 20180308164823.0 cr unu---uuuuu 161202e19960306xx s 000 0 eng 10.1093/jnci/88.5.279 doi (NATIONALLICENCE)oxford-10.1093/jnci/88.5.279 Role of c-myc in Tamoxifen-Induced Apoptosis in Estrogen-Independent Breast Cancer Cells [Elektronische Daten] [Yuan Kang, Robert Cortina, Roger R. Perry] 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<.05) and c-Myc protein threefold (from a relative immuno-fluorescence signal intensity of 28 ± 7 up to 83 ± 21; P<.05). The induction of c-myc by TAM was accompanied by internucleosomal DNA cleavage characteristic of apoptotic cell death. Addition of c-myc antisense oligonucleotide (5'-CACGTTGAGGGGCAT-3') to MDA-231 cells resulted in a nearly twofold decrease of basal c-myc mRNA (P<.05) and a sevenfold decrease of basal c-Myc protein (P<.05) expression. Addition of c-myc antisense oligomer also antagonized the TAM-induced increase in c-myc mRNA (P<.05) and protein expression (P<.05) and inhibited TAM-induced cytostasis (P<.01) and apoptosis. In parallel experiments, addition of the nonsense oligomer had no effect on any of the measured parameters. Conclusions These results indicate that the effects of TAM on ER-negative MDA-231 cells may be mediated through c-myc overexpression. c-myc may play a critical role in the growth and progression of MDA-231 breast cancer cells. [J Natl Cancer Inst 1996;88:279-84] © Oxford University Press REPORTS nationallicence Kang Yuan Division of Surgical Oncology, Eastern Virginia Medical School Norfolk aut Cortina Robert Division of Surgical Oncology, Eastern Virginia Medical School Norfolk aut Perry Roger R. Division of Surgical Oncology, Eastern Virginia Medical School Norfolk aut JNCI: Journal of the National Cancer Institute Oxford University Press 88/5(1996-03-06), 279-284 0027-8874 88:5<279 1996 88 jnci https://doi.org/10.1093/jnci/88.5.279 text/html Onlinezugriff via DOI 1 other jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jnci/88.5.279 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kang Yuan Division of Surgical Oncology, Eastern Virginia Medical School Norfolk aut NATIONALLICENCE 700 1- Cortina Robert Division of Surgical Oncology, Eastern Virginia Medical School Norfolk aut NATIONALLICENCE 700 1- Perry Roger R. Division of Surgical Oncology, Eastern Virginia Medical School Norfolk aut NATIONALLICENCE 773 0- JNCI: Journal of the National Cancer Institute Oxford University Press 88/5(1996-03-06), 279-284 0027-8874 88:5<279 1996 88 jnci Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford