Tamoxifen-induced activation of p21 (Waf1/Cip1) gene transcription is mediated by Early Growth Response-1 protein through the JNK and p38 MAP kinase/Elk-1 cascades in MDA-MB-361 breast carcinoma cells
- Authors
- Kim, Chang Gun; Choi, Byeong Hyeok; Son, Sang Wook; Yi, Seong Joon; Shin, Soon Young; Lee, Young Han
- Issue Date
- Jun-2007
- Publisher
- ELSEVIER SCIENCE INC
- Keywords
- tamoxifen; p2 (Waf1/Cip1); Egr-1; mitogen-activated protein kinase
- Citation
- CELLULAR SIGNALLING, v.19, no.6, pp 1290 - 1300
- Pages
- 11
- Indexed
- SCIE
SCOPUS
- Journal Title
- CELLULAR SIGNALLING
- Volume
- 19
- Number
- 6
- Start Page
- 1290
- End Page
- 1300
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/17940
- DOI
- 10.1016/j.cellsig.2007.01.008
- ISSN
- 0898-6568
1873-3913
- Abstract
- Tamoxifen (TAM) is a synthetic non-steroidal anti-estrogen compound that is widely used as an effective chemotherapeutic agent for treatment and prevention of breast cancer. Unfortunately, prolonged treatment with TAM causes TAM-responsive tumors to become TAM resistant through an as-yet-unknown mechanism. To develop novel anti-breast cancer agents that are therapeutically superior to TAM, we must first fully understand the biological effects of TAM. In this study, we found that TAM treatment of MDA-MB-361 breast cancer cells activated p21(Waf1/Cip1) gene transcription independently of p53. Furthermore, TAM-induced p21(Waf1/Cip1) promoter activity was enhanced by transient expression of the gene encoding Early Growth Response-1 (Egr-1) protein, a transcription factor that plays an important role in cell growth and differentiation. The TAM-induced p21(Waf1/Cip1) promoter activity was blocked by the expression of small interfering RNA (siRNA) targeted to Egr-1 mRNA. In addition, induction of Egr-1 expression by TAM occurred at the transcriptional level via Ets-domain transcription factor Elk-1 through the JNK and p38 mitogen-activated protein (MAP) kinase pathways. Inhibition of the JNK and p38 MAP kinase signals inhibited Egr-1-mediated p21(Waf1/Cip1) promoter activity. We conclude that TAM stimulation of p21(Waf1/Cip1) gene transcription in MDA-MB-361 cells depends largely on Elk-l-mediated Egr-1 expression induced by activation of the JNK and p38 MAP kinase pathways. (c) 2007 Elsevier Inc. All rights reserved.
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Collections - 2. Clinical Science > Department of Dermatology > 1. Journal Articles
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