Differential ability of antiestrogens to stimulate breast cancer cell (MCF-7) growth in vivo and in vitro

• Published in: Cancer research (Chicago, Ill.) Vol. 49; no. 17; pp. 4765 - 4769
• Main Authors: GOTTARDIS, M. M, WAGNER, R. J, BORDEN, E. C, JORDAN, V. C
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.09.1989
• Subjects: Animals; Biological and medical sciences; Estradiol - pharmacology; Female; Gynecology. Andrology. Obstetrics; Killer Cells, Natural - drug effects; Mammary gland diseases; Mammary Neoplasms, Experimental - immunology; Mammary Neoplasms, Experimental - pathology; Medical sciences; Mice; Mice, Nude; Neoplasm Transplantation; Rats; Rats, Nude; Tamoxifen - analogs & derivatives; Tamoxifen - pharmacology; Tumor Cells, Cultured; Tumors; Cell proliferation; Growth; Rodentia; Antiestrogen; Active immunity; In vitro; Tamoxifene; In vivo; Vertebrata; Chemotherapy; Mammalia; Cell line; Treatment; Mouse; Animal; Transplanted tumor; Tumor; Killer cell; Mammary gland; Mechanism of action; Tumor cell
• ISSN: 0008-5472; 1538-7445

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:C), were assayed for natural killer (NK) cell activity against 51Cr-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.