Paradoxical regulation of estrogen-dependent growth factor gene expression in estrogen receptor (ER)-negative human breast cancer cells stably expressing ER

Jeng, Meei-Huey; Jiang, Shun Yuan; Jordan, V. Craig

doi:10.1016/0304-3835(94)90001-9

Cited by 47 publications

(19 citation statements)

References 12 publications

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“…However, it is also known that E 2 itself at high concentrations could inhibit the growth of human breast cancer cells, apparently through ER-mediated signaling pathways [30][31][32]. Here it needs to be pointed out that while the weak growth-stimulatory effect of 2-MeO-E 2 is mediated by the ER, its predominant growth-inhibitory effect at high concentrations is not believed to be mediated by ER-signaling pathways.…”

Section: Discussionmentioning

confidence: 91%

Concentration-dependent mitogenic and antiproliferative actions of 2-methoxyestradiol in estrogen receptor-positive human breast cancer cells

Liu

Zhu

2004

The Journal of Steroid Biochemistry and Molecular Biology

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Section: Discussionmentioning

confidence: 91%

Concentration-dependent mitogenic and antiproliferative actions of 2-methoxyestradiol in estrogen receptor-positive human breast cancer cells

Liu

Zhu

2004

The Journal of Steroid Biochemistry and Molecular Biology

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“…This is in direct contrast to estrogen action in breast cancer cell lines where ERα-positive cells proliferate in response to estradiol (Allegra & Lippman 1978, Chalbos et al 1982. Furthermore, when ERα is introduced into ERα-negative cell lines, proliferation is often inhibited in response to estrogen and in many cases cell death results (Garcia et al 1992, Jiang & Jordan 1992, Jeng et al 1994, Levenson & Jordan 1994). There appears to be a fundamental difference between normal breast epithelium and breast cancer cell lines in their response to estrogen.…”

Section: Estrogen and Breast Cancermentioning

confidence: 86%

Estrogen receptor beta in breast cancer.

Palmieri

Cheng²,

Saji³

et al. 2002

Endocrine-Related Cancer

218

136

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Estrogen is essential for normal growth and differentiation in the mammary gland. It also supports growth of approximately 50% of primary breast cancers. For this reason, removal of estrogen or blocking of its action with the anti-estrogen, tamoxifen, is the main treatment for estrogen receptor alpha (ERα)-positive tumors. In 1996, when oncologists became aware of a second ER, ERβ, there was some doubt as to whether this receptor would be of importance in breast cancer because the clinical consensus was that responsiveness to tamoxifen is related to the presence of ERα in breast cancer. Today we know that ERα and ERβ have distinct cellular distributions, regulate separate sets of genes and can oppose each other's actions on some genes. We also know that ERβ is widely expressed in both the normal and malignant breast and that there are proliferating cells in the breast which express ERβ. In this review we summarize what is known about ERβ in breast cancer and examine the possibility that ERβ-selective ligands may well represent a useful class of pharmacological tools with a novel target, namely proliferating cells expressing ERβ.

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“…Estrogens and anti-estrogens unfortunately had an opposite effect on growth in naturally ERpositive breast cancer cells like MCF7 and in ER-negative breast cancer cells transfected with ERα like MDA-MB231 cells. However, the transcriptional activity of reporter genes was stimulated by estrogen in both types of cancer and some endogenous estrogen-regulated genes were also stimulated by estradiol after ER transfection (Touitou et al 1990, Jeng et al 1994. Understanding the difference in the two cell types (ER-negative or ER-positive) responsible for the inverse effect of activated ER may provide a clue for developing new targeted therapy aimed at replacing ER in order to inhibit the factor involved in the stimulation of proliferation and invasion in ER-negative breast cancers.…”

Section: To Transform Er-negative Into Er-positive Breast Cancer Cellsmentioning

confidence: 99%

How to target estrogen receptor-negative breast cancer?

Rochefort

Glondu²,

Sahla³

et al. 2003

Endocrine-Related Cancer

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Estrogen receptor (ER)-positive breast cancers generally have a better prognosis and are often responsive to anti-estrogen therapy, which is the first example of a successful therapy targeted on a specific protein, the ER. Unfortunately ER-negative breast cancers are more aggressive and unresponsive to anti-estrogens. Other targeted therapies are thus urgently needed, based on breast cancer oncogene inhibition or suppressor gene activation as far as molecular studies have demonstrated the alteration of expression, or structure of these genes in human breast cancer. Using the MDA-MB.231 human breast cancer cell line as a model of ER-negative breast cancers, we are investigating two of these approaches in our laboratory. Our first approach was to transfect the ER or various ER-deleted variants into an ER-negative cell line in an attempt to recover anti-estrogen responsiveness. The unliganded receptor, and surprisingly estradiol, were both found to inhibit tumor growth and invasiveness in vitro and in vivo. The mechanisms of these inhibitions in ER-negative cancer cells are being studied, in an attempt to target the ER sequence responsible for such inhibition in these cancer cells. Another strategy is trying to inhibit the activity or expression of an oncogene specifically overexpressed in most breast cancers. This approach was recently shown by others to be efficient in breast cancer therapy with HER2-Neu oncogene amplification using Herceptin. Without excluding other molecular putative targets, we have focused our research on cathepsin D as a potential target, since it is often overexpressed in aggressive human breast cancers, including ER-negative tumors, and rarely associated with HER2-Neu amplification. Our first results obtained in vitro on cell lines and in vivo in tumor xenografts in nude mice, illustrate that the mode of action of cathepsin D in breast cancer is useful to guide the development of these therapies. In the past 20 years we have learned that the action of cathepsin D is complex and involves both intracellular and extracellular activities due to its proteolytic activity and to interactions with membrane components without catalytic activity. Each of these mechanisms could be potentially inhibited in an attempt to prevent tumor growth. Breast cancer is a very heterogeneous and multigenic disease and different targeted therapies adapted to each category of breast cancer are therefore required. Validated assays in the primary tumor of molecular markers such as ER, HER2-Neu and cathepsin D should help to predict which targeted therapy should be applied to cure breast cancer patients.

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Paradoxical regulation of estrogen-dependent growth factor gene expression in estrogen receptor (ER)-negative human breast cancer cells stably expressing ER

Cited by 47 publications

References 12 publications

Concentration-dependent mitogenic and antiproliferative actions of 2-methoxyestradiol in estrogen receptor-positive human breast cancer cells

Concentration-dependent mitogenic and antiproliferative actions of 2-methoxyestradiol in estrogen receptor-positive human breast cancer cells

Estrogen receptor beta in breast cancer.

How to target estrogen receptor-negative breast cancer?

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