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

Clarke, R., Skaar, T., Baumann, K., Leonessa, F., James, M., Lippman, J., Thompson, E.W., Freter, C., & Brunner, N. (1994) Hormonal carcinogenesis in breast cancer : cellular and molecular studies of malignant progression. Breast Cancer Research and Treatment, 31(2-3), pp. 237-248.

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Abstract

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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50 citations in Scopus
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50 citations in Web of Science®

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ID Code: 71741
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By (since 1996):49
Export Date: 6 May 2014
Source: Scopus
PubMed ID: 7881102
Additional URLs:
Keywords: breast cancer, carcinogenesis, estrogen, hormone dependence, malignant progression
DOI: 10.1007/BF00666157
ISSN: 1573-7217
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Deposited On: 16 May 2014 04:18
Last Modified: 16 May 2014 04:18

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