PMID:8402691

Citation	Zajchowski, DA, Sager, R and Webster, L (1993) Estrogen inhibits the growth of estrogen receptor-negative, but not estrogen receptor-positive, human mammary epithelial cells expressing a recombinant estrogen receptor. Cancer Res. 53:5004-11
Abstract	Estrogen is essential for the growth of the normal mammary gland and most estrogen receptor (ER)-positive mammary carcinomas. To better understand the differences between the estrogen response pathways in normal and tumor cells, we have stably transfected ER-negative immortal, nontumorigenic human mammary epithelial cells and ER-negative breast cancer cells with an ER-encoding expression vector. Unexpectedly, estrogen treatment (1.0 nM) inhibited the proliferation of ER-transfected nontumorigenic and tumor-derived cells. The control transfectants and parental cells exhibited no response to estrogen concentrations as high as 1.0 microM. This inhibitory effect was attributed to a decreased growth rate and a perturbation of the cell cycle distribution by estrogen treatment of the ER transfectants. The inhibitory response was blocked by cotreatment with the antiestrogen ICI 164,384 as predicted for a pure antagonist of estrogen action. However, treatment with the antiestrogen hydroxytamoxifen caused growth inhibition, implying that hydroxytamoxifen acts as an agonist of estrogen action in ER-transfected cells. Since estrogen is a mitogenic and not a growth-inhibitory stimulus for ER-positive breast cancers and cell lines, we tested the effect of constitutive, high level expression of the ER in ER-positive tumor cells. Stable transfection of ER-positive MCF-7 and T47D cells with the ER expression vector yielded cells with varying amounts of ER. At ER levels comparable to those found in the ER-negative transfected cells, the MCF-7 and T47D ER transfectants were not inhibited by estrogen. These data suggest that ER-positive breast cancer cells can tolerate higher constitutive levels of ER expression than ER-negative cells. The mechanism by which this is accomplished may be an essential step in the process which yields ER-positive tumors.
Links	PubMed
Keywords	Animals; Breast/cytology; Breast/metabolism; Breast Neoplasms/metabolism; Breast Neoplasms/pathology; Cell Cycle/drug effects; Cell Division/drug effects; Cell Line; Dose-Response Relationship, Drug; Epithelial Cells; Epithelium/drug effects; Epithelium/metabolism; Estradiol/analogs & derivatives; Estradiol/metabolism; Estradiol/pharmacology; Estrogen Antagonists/pharmacology; Female; Humans; Kinetics; Mice; Mice, Nude; Polyunsaturated Alkamides; Receptors, Estrogen/analysis; Receptors, Estrogen/biosynthesis; Recombinant Proteins/biosynthesis; Tamoxifen/analogs & derivatives; Tamoxifen/pharmacology; Transfection; Transplantation, Heterologous; Tumor Cells, Cultured
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:ESR1		GO:0071391 : cellular response to estrogen stimulus	ECO:0000314:		P		Table 3 and Table 2 show the effect of estrogen on estrogen receptors and the cell cycle of cells given estrogen. Figure 4 shows the colony growth of the cells in relation to the concentration of estrogen.	complete CACAO 3328

References

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