Hormonal carcinogenesis in breast cancer

cellular and molecular studies of malignant progression

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

Research output: Contribution to journalArticle

53 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)237-248
Number of pages12
JournalBreast Cancer Research and Treatment
Volume31
Issue number2-3
DOIs
StatePublished - Jan 1994
Externally publishedYes

Fingerprint

MCF-7 Cells
Estrogens
Carcinogenesis
Hormones
Breast Neoplasms
Estrogen Receptor Modulators
Progesterone Receptors
Tamoxifen
Nude Mice
Laminin Receptors
Genes
Cell Line
Cathepsin D
Gene Regulatory Networks
Epidermal Growth Factor Receptor
Estrogen Receptors
Adipose Tissue
Breast
Neoplasms

Keywords

  • breast cancer
  • carcinogenesis
  • estrogen
  • hormone dependence
  • malignant progression

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Hormonal carcinogenesis in breast cancer : cellular and molecular studies of malignant progression. / Clarke, Robert; Skaar, Todd; Baumann, Klaus; Leonessa, Fabio; James, Mattie; Lippman, Jeremy; Thompson, Erik W.; Freter, Carl; Brunner, Nils.

In: Breast Cancer Research and Treatment, Vol. 31, No. 2-3, 01.1994, p. 237-248.

Research output: Contribution to journalArticle

Clarke, R, Skaar, T, Baumann, K, Leonessa, F, James, M, Lippman, J, Thompson, EW, Freter, C & Brunner, N 1994, 'Hormonal carcinogenesis in breast cancer: cellular and molecular studies of malignant progression', Breast Cancer Research and Treatment, vol. 31, no. 2-3, pp. 237-248. https://doi.org/10.1007/BF00666157
Clarke, Robert ; Skaar, Todd ; Baumann, Klaus ; Leonessa, Fabio ; James, Mattie ; Lippman, Jeremy ; Thompson, Erik W. ; Freter, Carl ; Brunner, Nils. / Hormonal carcinogenesis in breast cancer : cellular and molecular studies of malignant progression. In: Breast Cancer Research and Treatment. 1994 ; Vol. 31, No. 2-3. pp. 237-248.
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