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Hormonal carcinogenesis in breast cancer: cellular and molecular studies of malignant progression

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Summary

We have established and characterized a series of variant cell lines in which to identify the critical factors associated with E2-induced malignant progression, and the acquisition to tamoxifen resistance in human breast cancer. Sublines of the hormone-dependent MCF-7 cell line (MCF7/MIII and MCF7/LCC1) form stable, invasive, estrogen independent tumors in the mammary fat pads of ovariectomized athymic nude mice. These cells retain expression of both estrogen (ER) and progesterone receptors (PGR), but retain sensitivity to each of the major structural classes of antiestrogens. The tamoxifen-resistant MCF7/LCC2 cells retain sensitivity to the inhibitory effects of the steroidal antiestrogen ICI 182780. By comparing the parental hormone-dependent and variant hormone-independent cells, we have demonstrated an altered expression of some estrogen regulated genes (PGR, pS2, cathepsin D) in the hormone-independent variants. Other genes remain normally estrogen regulated (ER, laminin receptor, EGF-receptor). These data strongly implicate the altered regulation of a specific subset or network of estrogen regulated genes in the malignant progression of human breast cancer. Some of the primary response genes in this network may exhibit dose-response and induction kinetics similar to pS2, which is constitutively upregulated in the MCF7/MIII, MCF7/LCC1 and MCF7/LCC2 cells.

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Authors and Affiliations

  1. Room S128A, Vincent T. Lombardi Cancer Research Center, Georgetown University Medical School, 3800 Reservoir Rd NW, 20007, Washington, DC, USA

    Robert Clarke, Todd Skaar, Klaus Baumann, Fabio Leonessa, Mattie James, Jeremy Lippman, Erik W. Thompson, Carl Freter & Nils Brunner

  2. Department of Physiology & Biophysics, Georgetown University Medical School, 3800 Reservoir Rd NW, 20007, Washington, DC, USA

    Robert Clarke

  3. Department of Cell Biology, Georgetown University Medical School, 3800 Reservoir Rd NW, 20007, Washington, DC, USA

    Erik W. Thompson

  4. Finsen Laboratory, Strandboulevarden Copenhagen, Denmark

    Nils Brunner

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  1. Robert Clarke
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Clarke, R., Skaar, T., Baumann, K. et al. Hormonal carcinogenesis in breast cancer: cellular and molecular studies of malignant progression. Breast Cancer Res Tr 31, 237–248 (1994). https://doi.org/10.1007/BF00666157

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