Estrogen regulation of cell proliferation and distribution of estrogen receptor-α in the brains of adult female prairie and meadow voles

A fraction of the nuclear estrogen receptor α (ERα) is localized to the plasma membrane region of 17β-estradiol (E2) target cells. We previously reported that ERα is a palmitoylated protein. To gain insight into the molecular mechanism of ERα residence at the plasma membrane, we tested both the role of palmitoylation and the impact of E2 stimulation on ERα membrane localization. The cancer cell lines expressing transfected or endogenous human ERα (HeLa and HepG2, respectively) or the ERα nonpalmitoylable Cys447Ala mutant transfected in HeLa cells were used as experimental models. We found that palmitoylation of ERα enacts ERα association with the plasma membrane, interaction with the membrane protein caveolin-1, and nongenomic activities, including activation of signaling pathways and cell proliferation (i.e., ERK and AKT activation, cyclin D1 promoter activity, DNA synthesis). Moreover, E2 reduces both ERα palmitoylation and its interaction with caveolin-1, in a time- and dose-dependent manner. These data point to the physiological role of ERα palmitoylation in the receptor localization to the cell membrane and in the regulation of the E2-induced cell proliferation.

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Delayed activation of extracellular-signal-regulated kinase 1/2 is involved in genistein- and equol-induced cell proliferation and estrogen-receptor-α-mediated transcription in MCF-7 breast cancer cells

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2009.01.016 ◽

2010 ◽

Vol 21 (5) ◽

pp. 390-396 ◽

Cited By ~ 21

Author(s):

Huaqing Liu ◽

Juan Du ◽

Chunyan Hu ◽

Hong Qi ◽

Xinru Wang ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Estrogen Receptor ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Estrogen Receptor Α ◽

Extracellular Signal Regulated Kinase ◽

Extracellular Signal ◽

Mcf 7

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Estrogenic Activity of Mycoestrogen (3β,5α,22E)-Ergost-22-en-3-ol via Estrogen Receptor α-Dependent Signaling Pathways in MCF-7 Cells

Molecules ◽

10.3390/molecules27010036 ◽

2021 ◽

Vol 27 (1) ◽

pp. 36

Author(s):

Dahae Lee ◽

Yuri Ko ◽

Changhyun Pang ◽

Yoon-Joo Ko ◽

You-Kyoung Choi ◽

...

Keyword(s):

Cell Proliferation ◽

Estrogen Receptor ◽

Methanol Extract ◽

Estrogenic Activity ◽

Cancer Cell Line ◽

Estrogen Receptor Α ◽

Bile Secretion ◽

Bioassay Guided Fractionation ◽

Positive Breast Cancer Cell ◽

Mcf 7

Armillariella tabescens (Scop.) Sing., a mushroom of the family Tricholomataceae, has been used in traditional oriental medicine to treat cholecystitis, improve bile secretion, and regulate bile-duct pressure. The present study evaluated the estrogen-like effects of A. tabescens using a cell-proliferation assay in an estrogen-receptor-positive breast cancer cell line (MCF-7). We found that the methanol extract of A. tabescens fruiting bodies promoted cell proliferation in MCF-7 cells. Using bioassay-guided fractionation of the methanol extract and chemical investigation, we isolated and identified four steroids and four fatty acids from the active fraction. All eight compounds were evaluated by E-screen assay for their estrogen-like effects in MCF-7 cells. Among the tested isolates, only (3β,5α,22E)-ergost-22-en-3-ol promoted cell proliferation in MCF-7 cells; this effect was mitigated by the ER antagonist, ICI 182,780. The mechanism underlying the estrogen-like effect of (3β,5α,22E)-ergost-22-en-3-ol was evaluated using Western blot analysis to detect the expression of extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), Akt, and estrogen receptor α (ERα). We found that (3β,5α,22E)-ergost-22-en-3-ol induced an increase in phosphorylation of ERK, PI3K, Akt, and ERα. Together, these experimental results suggest that (3β,5α,22E)-ergost-22-en-3-ol is responsible for the estrogen-like effects of A. tabescens and may potentially aid control of estrogenic activity in menopause.

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