Differential Regulation of Growth and Invasiveness of MCF-7 Breast Cancer Cells by Antiestrogens

Erik W. Thompson, Reuven Reich, Thomas B. Shima, Adriana Albini, Jeannette Graf, George R. Martin, Robert B. Dickson, Marc E. Lippman

Research output: Contribution to journalArticlepeer-review

133 Scopus citations

Abstract

Estrogen increases the ability of the estrogen-dependent MCF-7 human breast cancer cell line to both proliferate and invade through an artificial basement membrane. In studying the response of MCF-7 cells to various antiestrogens, we found that 4-hydroxytamoxifen and tamoxifen inhibited cell proliferation but increased their invasiveness. In contrast, the structurally unrelated benzothiophene antiestrogens, LY117018 and LY156758, were potent antiproliferative agents which did not stimulate invasiveness. The differential effects of these antiestrogenic agents on invasion correlated with changes in production of collagenase IV, while no significant change was seen in the chemotactic activity of the cells. Invasiveness was increased by 170-estradiol or 4-hydroxytamoxifen after a few hours of treatment and was rapidly lost when 170-estradiol was withdrawn. Stimulation of invasiveness with 170-estradiol was blocked by the antiestrogen, LY117018. Cells from the MDA-MB-231 line which lacks estrogen receptors were not affected by estrogen or antiestrogen in terms of proliferation or invasion. These studies indicate that the invasiveness of MCF-7 cells is regulated by antiestrogens through the estrogen receptor and may be mediated by collagenase IV activity. Antiestrogens which reduce both the proliferation and invasiveness of these cells may be interesting new candidates for clinical application.

Original languageEnglish
Pages (from-to)6764-6768
Number of pages5
JournalCancer Research
Volume48
Issue number23
StatePublished - 1988
Externally publishedYes

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