Abstract
In an attempt to approach the mechanism by which estrogen and antiestrogen regulate the growth of estrogen receptor-positive breast cancer, we have studied the effects of the antiestrogens tamoxifen (TAM) and 4-hydroxytamoxifen (OH-TAM) on the induction of two estrogen-specific proteins in a variant of MCF7 cells termed R27, cloned for its ability to grow in the presence of TAM. We found that, in the R27 variant, antiestrogens as well as estradiol were able to increase specifically the production of a M(r) 52,000 protein which was released into the culture medium. This protein was shown to be identical to the M(r) 52,000 glycoprotein induced by estrogen and released by MCF7 cells on the basis of its specific inducibility by physiological concentrations of 17β-estradiol and of its resolution in two-dimensional gel analysis. Dose-response analysis showed that, in the R27 variant, TAM and OH-TAM acquired the ability to induce the M(r) 52,000 protein at concentrations compatible with their relative affinities for the estrogen receptor, while these antiestrogens were inefficient in the wild MCF7 cells. Whereas the relative increase of the M(r) 52,000 protein was similar with TAM, OH-TAM, and 17β-estradiol, the general production of M(r) 52,000 and of total labelled proteins was less with the antiestrogens than with 17β-estradiol. Moreover, OH-TAM displayed a biphasic dose-response curve with inhibitory effects at concentrations above 10 nM, suggesting an additional mechanism. Neither TAM nor OH-TAM had any antiestrogenic effect when added in the presence of 17β-estradiol. In the R27 variant, both estradiol and antiestrogens induced the progesterone receptor sites; however, the extent of the stimulation was lower with antiestrogens than with estradiol. This study shows that, in addition to the classical antiestrogen-resistant breast cancer cells, in which the estrogen receptor is absent or inactive, there is another class of antiestrogen-resistant cells in which the drug becomes a full estrogen agonist as evidenced by the induction of the M(r) 52,000 estrogen-specific protein, which is not induced in the wild-type cells.
| Original language | English |
|---|---|
| Pages (from-to) | 2084-2088 |
| Number of pages | 5 |
| Journal | Cancer Research |
| Volume | 44 |
| Issue number | 5 |
| State | Published - Jul 5 1984 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Induction of two estrogen-responsive proteins by antiestrogens in R27, a tamoxifen-resistant clone of MCF7 cells. / Vignon, F.; Lippman, Marc E; Nawata, H.; Derocq, D.; Rochefort, H.
In: Cancer Research, Vol. 44, No. 5, 05.07.1984, p. 2084-2088.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Induction of two estrogen-responsive proteins by antiestrogens in R27, a tamoxifen-resistant clone of MCF7 cells
AU - Vignon, F.
AU - Lippman, Marc E
AU - Nawata, H.
AU - Derocq, D.
AU - Rochefort, H.
PY - 1984/7/5
Y1 - 1984/7/5
N2 - In an attempt to approach the mechanism by which estrogen and antiestrogen regulate the growth of estrogen receptor-positive breast cancer, we have studied the effects of the antiestrogens tamoxifen (TAM) and 4-hydroxytamoxifen (OH-TAM) on the induction of two estrogen-specific proteins in a variant of MCF7 cells termed R27, cloned for its ability to grow in the presence of TAM. We found that, in the R27 variant, antiestrogens as well as estradiol were able to increase specifically the production of a M(r) 52,000 protein which was released into the culture medium. This protein was shown to be identical to the M(r) 52,000 glycoprotein induced by estrogen and released by MCF7 cells on the basis of its specific inducibility by physiological concentrations of 17β-estradiol and of its resolution in two-dimensional gel analysis. Dose-response analysis showed that, in the R27 variant, TAM and OH-TAM acquired the ability to induce the M(r) 52,000 protein at concentrations compatible with their relative affinities for the estrogen receptor, while these antiestrogens were inefficient in the wild MCF7 cells. Whereas the relative increase of the M(r) 52,000 protein was similar with TAM, OH-TAM, and 17β-estradiol, the general production of M(r) 52,000 and of total labelled proteins was less with the antiestrogens than with 17β-estradiol. Moreover, OH-TAM displayed a biphasic dose-response curve with inhibitory effects at concentrations above 10 nM, suggesting an additional mechanism. Neither TAM nor OH-TAM had any antiestrogenic effect when added in the presence of 17β-estradiol. In the R27 variant, both estradiol and antiestrogens induced the progesterone receptor sites; however, the extent of the stimulation was lower with antiestrogens than with estradiol. This study shows that, in addition to the classical antiestrogen-resistant breast cancer cells, in which the estrogen receptor is absent or inactive, there is another class of antiestrogen-resistant cells in which the drug becomes a full estrogen agonist as evidenced by the induction of the M(r) 52,000 estrogen-specific protein, which is not induced in the wild-type cells.
AB - In an attempt to approach the mechanism by which estrogen and antiestrogen regulate the growth of estrogen receptor-positive breast cancer, we have studied the effects of the antiestrogens tamoxifen (TAM) and 4-hydroxytamoxifen (OH-TAM) on the induction of two estrogen-specific proteins in a variant of MCF7 cells termed R27, cloned for its ability to grow in the presence of TAM. We found that, in the R27 variant, antiestrogens as well as estradiol were able to increase specifically the production of a M(r) 52,000 protein which was released into the culture medium. This protein was shown to be identical to the M(r) 52,000 glycoprotein induced by estrogen and released by MCF7 cells on the basis of its specific inducibility by physiological concentrations of 17β-estradiol and of its resolution in two-dimensional gel analysis. Dose-response analysis showed that, in the R27 variant, TAM and OH-TAM acquired the ability to induce the M(r) 52,000 protein at concentrations compatible with their relative affinities for the estrogen receptor, while these antiestrogens were inefficient in the wild MCF7 cells. Whereas the relative increase of the M(r) 52,000 protein was similar with TAM, OH-TAM, and 17β-estradiol, the general production of M(r) 52,000 and of total labelled proteins was less with the antiestrogens than with 17β-estradiol. Moreover, OH-TAM displayed a biphasic dose-response curve with inhibitory effects at concentrations above 10 nM, suggesting an additional mechanism. Neither TAM nor OH-TAM had any antiestrogenic effect when added in the presence of 17β-estradiol. In the R27 variant, both estradiol and antiestrogens induced the progesterone receptor sites; however, the extent of the stimulation was lower with antiestrogens than with estradiol. This study shows that, in addition to the classical antiestrogen-resistant breast cancer cells, in which the estrogen receptor is absent or inactive, there is another class of antiestrogen-resistant cells in which the drug becomes a full estrogen agonist as evidenced by the induction of the M(r) 52,000 estrogen-specific protein, which is not induced in the wild-type cells.
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M3 - Article
VL - 44
SP - 2084
EP - 2088
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 5
ER -