TY - JOUR
T1 - Estrogen increases intracellular p26Bcl-2 to p21Bax ratios and inhibits taxol-induced apoptosis of human breast cancer MCF-7 cells
AU - Huang, Yue
AU - Ray, Swapan
AU - Reed, John C.
AU - Ibrado, Ana Maria
AU - Tang, Caroline
AU - Nawabi, Amir
AU - Bhalla, Kapil
N1 - Funding Information:
This work was support by the NCI/NIH grants CA63382 and CA56613. John C. Reed and Kapil Bhalla are scholars of the Leukemia Society of America.
PY - 1997
Y1 - 1997
N2 - Recent studies have demonstrated that following estrogen ablation, estrogen responsive breast cancer cells undergo apoptosis. In addition, estrogen receptor (ER) expression has been strongly correlated with the expression of the bcl-2 gene product, p26Bcl-2 protein, which is known to inhibit apoptosis. In the present studies, we investigated whether estrogen affects the intracellular levels of p26Bcl-2 and thereby modulates taxol-induced apoptosis of estrogen responsive human breast cancer MCF-7 cells. Transfer of MCF-7 cells to a culture-medium without estrogens reduced their intracellular p26Bcl-2 levels by 50%. Inclusion of 0.1 μM estradiol in the medium produced approximately a four-fold increase in p26Bcl-2, but not p29Bcl-x(L), or p21Bax levels; the expression of the c-myc and mdr-1 genes remained unchanged. Estradiol-induced fourfold increase in the ratio of the p26Bcl-2 to p21Bax levels caused a significant decline in the lethal, kilobase size DNA fragments of apoptosis, which had resulted when MCF-7 cells were cultured in a medium without estrogen. In addition, in MCF-7 cells, estradiol-induced increase in the intracellular p26Bcl-2 to p21Bax ratios was associated with a significant reduction in the large-sized DNA fragmentation induced by treatment with taxol. The increased ratios also protected MCF-7 cells against taxol-mediated cytotoxicity as assessed by the MTT assay. These results suggest that by modulating p26Bcl-2 levels, estrogens may affect the antitumor activity of taxol and potentially of other anti-breast cancer drugs against estrogen responsive human breast cancer cells.
AB - Recent studies have demonstrated that following estrogen ablation, estrogen responsive breast cancer cells undergo apoptosis. In addition, estrogen receptor (ER) expression has been strongly correlated with the expression of the bcl-2 gene product, p26Bcl-2 protein, which is known to inhibit apoptosis. In the present studies, we investigated whether estrogen affects the intracellular levels of p26Bcl-2 and thereby modulates taxol-induced apoptosis of estrogen responsive human breast cancer MCF-7 cells. Transfer of MCF-7 cells to a culture-medium without estrogens reduced their intracellular p26Bcl-2 levels by 50%. Inclusion of 0.1 μM estradiol in the medium produced approximately a four-fold increase in p26Bcl-2, but not p29Bcl-x(L), or p21Bax levels; the expression of the c-myc and mdr-1 genes remained unchanged. Estradiol-induced fourfold increase in the ratio of the p26Bcl-2 to p21Bax levels caused a significant decline in the lethal, kilobase size DNA fragments of apoptosis, which had resulted when MCF-7 cells were cultured in a medium without estrogen. In addition, in MCF-7 cells, estradiol-induced increase in the intracellular p26Bcl-2 to p21Bax ratios was associated with a significant reduction in the large-sized DNA fragmentation induced by treatment with taxol. The increased ratios also protected MCF-7 cells against taxol-mediated cytotoxicity as assessed by the MTT assay. These results suggest that by modulating p26Bcl-2 levels, estrogens may affect the antitumor activity of taxol and potentially of other anti-breast cancer drugs against estrogen responsive human breast cancer cells.
KW - Apoptosis
KW - Bax
KW - Bcl-2
KW - Breast cancer
KW - Estradiol
KW - Taxol
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U2 - 10.1023/A:1005777219997
DO - 10.1023/A:1005777219997
M3 - Article
C2 - 9116321
AN - SCOPUS:0031018983
SN - 0167-6806
VL - 42
SP - 73
EP - 81
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 1
ER -