TY - JOUR
T1 - Differential Ability of Antiestrogens to Stimulate Breast Cancer Cell (MCF-7) Growth in Vivo and in Vitro
AU - Gottardis, Marco M.
AU - Wagner, Randall J.
AU - Borden, Ernest C.
AU - Jordan, V. Craig
PY - 1989/9/1
Y1 - 1989/9/1
N2 - We have previously described an MCF-7 breast cancer cell variant, MCF-7TAM, which is stimulated to grow in athymic mice by tamoxifen (TAM) (M. M. Gottardis and V. C. Jordan, Cancer Res., 48:5183–5187, 1988). Earlier experiments have shown that TAM exhibits some profound estrogen-like effects in mice whereas TAM is less estrogenic in the rat. The aim in these studies was to compare the ability of MCF-7TAM to grow in different host environments and to determine whether the TAM-stimulated phenotype could be maintained in vitro. Ovariectomized athymic mice and rats were implanted with 1-mm3 pieces of MCF-7TAM tumor and treated with estradiol, TAM, or control silastic capsules. After 9 weeks of growth in either species, TAM or estradiol-treated groups both had sustained growth of MCF-7TAM compared with the control groups. To determine the effects of estradiol and TAM on immune function in athymic mice, splenocytes from treated or control athymic mice, challenged with poly(I:Q, were assayed for natural killer (NK) cell activity against slCr-labeled YAC1 target cells. Both estradiol and TAM abolished lytic activity by 12 weeks of treatment. To evaluate the role of a decrease in NK-cell activity in the host on growth of MCF-7TAM xenografts we compared the growth effects in athymic and NK-cell deficient, ovariectomized beige mice. TAM stimulated MCF-7TAM in both beige and athymic mice; however, the tumor grew more rapidly in control beige mice than in control athymic mice. This study demonstrated that TAM-stimulated growth could occur in vivo. However, TAM or 4-hydroxytamoxifen did not cause a stimulation of MCF-7TAM compared with wild-type MCF-7 cells when experiments were conducted in vitro. These studies demonstrate that a suppression immune function can facilitate the growth of MCF-7TAM in athymic animals. However, additional components of the host environment contribute to TAM-stimulated growth in vivo.
AB - We have previously described an MCF-7 breast cancer cell variant, MCF-7TAM, which is stimulated to grow in athymic mice by tamoxifen (TAM) (M. M. Gottardis and V. C. Jordan, Cancer Res., 48:5183–5187, 1988). Earlier experiments have shown that TAM exhibits some profound estrogen-like effects in mice whereas TAM is less estrogenic in the rat. The aim in these studies was to compare the ability of MCF-7TAM to grow in different host environments and to determine whether the TAM-stimulated phenotype could be maintained in vitro. Ovariectomized athymic mice and rats were implanted with 1-mm3 pieces of MCF-7TAM tumor and treated with estradiol, TAM, or control silastic capsules. After 9 weeks of growth in either species, TAM or estradiol-treated groups both had sustained growth of MCF-7TAM compared with the control groups. To determine the effects of estradiol and TAM on immune function in athymic mice, splenocytes from treated or control athymic mice, challenged with poly(I:Q, were assayed for natural killer (NK) cell activity against slCr-labeled YAC1 target cells. Both estradiol and TAM abolished lytic activity by 12 weeks of treatment. To evaluate the role of a decrease in NK-cell activity in the host on growth of MCF-7TAM xenografts we compared the growth effects in athymic and NK-cell deficient, ovariectomized beige mice. TAM stimulated MCF-7TAM in both beige and athymic mice; however, the tumor grew more rapidly in control beige mice than in control athymic mice. This study demonstrated that TAM-stimulated growth could occur in vivo. However, TAM or 4-hydroxytamoxifen did not cause a stimulation of MCF-7TAM compared with wild-type MCF-7 cells when experiments were conducted in vitro. These studies demonstrate that a suppression immune function can facilitate the growth of MCF-7TAM in athymic animals. However, additional components of the host environment contribute to TAM-stimulated growth in vivo.
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M3 - Article
C2 - 2758410
AN - SCOPUS:0024316533
SN - 0008-5472
VL - 49
SP - 4765
EP - 4769
JO - Cancer Research
JF - Cancer Research
IS - 17
ER -