J Korean Cancer Assoc.
2000 Jun;32(3):531-538.
The Role of bcl-2 and p53 in Tamoxifen-Induced Apoptosis
of Human Breast Cancer Cell Lines
- Affiliations
-
- 1Departments of Surgery, Korea Cancer Center Hospital.
- 2Departments of Laboratory of Molecular Oncology, Korea Cancer Center Hospital.
- 3Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
Abstract
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PURPOSE: Tamoxifen has been well known as an effective anti-tumor agent against breast cancer.
The important role of bcl-2 and p53 proteins in tamoxifen-induced apoptosis of breast cancer
cells has been suggested. However, the paradoxical fact that bcl-2 over-expression is assdegrees Ciated
with better prognosis in clinic has not yet been clearly explained. To investigate this paradox,
we analyzed the effect and dynamics of bcl-2 and p53 on the apoptosis after treatment of breast
cancer cells with tamoxifen.
MATERIALS AND METHODS
The human breast cancer cell lines MCF-7 and MB MDA-468 were
treated with 17-betaestradiol (E2) and tamoxifen.
RESULTS
Following tamoxifen treatment, MCF-7 cells underwent apoptosis accompanied by
reduced bcl-2 expression. E2 pre-treatment led to the inhibition of tamoxifen-mediated apoptosis
and bcl-2 down-regulation. When MB MDA-468 cells were treated with E2 or tamoxifen, bcl-2
and p53 protein expression did not change and apoptosis did not develop.
CONCLUSION
We observed that the down-regulation of bcl-2 by tamoxifen treatment can facilitate
the apoptosis of breast cancer cells without p53 mutations. This finding was consistent with
clinical experiences in which bcl-2 positive tumors were assdegrees Ciated with more indolent phenotypes
in breast cancer.