Min Cheul So; Hong Pil Hwang; Chang Ho Lee; Hyun Jo Youn; Sung Hoo Jung; Jae Cheun Kim

doi:10.4048/jbc.2006.9.2.91

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So, Hwang, Lee, Youn, Jung, and Kim: Up-regulation of Pi3k/Akt Signaling by 17β-estradiol through Activation Of Estrogen Receptor-α in Breast Cancer Cells

Original Article

Journal of Breast Cancer

Journal of Breast Cancer 2006; 9(2): 91-97.

Published online: 30 June 2006

DOI: https://doi.org/10.4048/jbc.2006.9.2.91

Up-regulation of Pi3k/Akt Signaling by 17β-estradiol through Activation Of Estrogen Receptor-α in Breast Cancer Cells

Min Cheul So, Hong Pil Hwang, Chang Ho Lee, Hyun Jo Youn, Sung Hoo Jung, Jae Cheun Kim

Division of Breast · Endocrine Surgery, Department of Surgery, Chonbuk National University Medical School, Jeonju, Korea.

Correspondence to: Sung Hoo Jung. Department of Surgery, Chonbuk National University Hospital, 634-18 Geumam-dong, Deokjin-ku, Jeonju 561-712, Korea. Tel: 063-250-2133, Fax: 063-271-6197, shjung@chonbuk.ac.kr

Received 17 January 2006 Accepted 22 May 2006

Abstract

Purpose

Estrogen stimulates cell proliferation in breast cancer, the biological effects of which are mediated through two intracellular receptors: estrogen receptor-alpha (ERα) and estrogen receptor-beta (ERβ). However, the actual role of ERs in the proliferative action of estrogen remains to be established. It was recently found that ER activates phosphatidylinositol-3-OH kinase (PI3K), via its binding with the p85 regulatory subunit of PI3K. Therefore, possible mechanisms may include ER-mediated phosphoinositide metabolism, with the subsequent formation of phosphatidylinositol-3, 4, 5-trisphosphate (PIP₃), which is generated from phosphatidylinositol 4, 5-bisphosphate (PIP₂) via PI3K activation. The present study has demonstrated that 17b-estradiol (E2) up-regulates PI3K in an ERα, but not an ERβ dependent manner, and also stimulates cell growth in breast cancer cells.

Methods

To study this phenomenon, we treated ER-positive MCF-7 cells and ERα-negative MDA-MB-231 cells with 10 nM E2.

Results

The treatment of MCF-7 cells with E2 resulted in a marked increase in the expression of PI3K (p85), which was paralleled by increases in the levels of phospho-Akt (Ser-473) and PIP3. These observations were also correlated with increased E2-induced cell proliferation activity. However, no effects of E2 on breast cancer cells were observed in the MDA-MB-231 cell line, indicating the pathway of E2-mediated up-regulation of PI3K/Akt is ERα-dependent.

Conclusion

These results suggest that estrogen activates PI3K/Akt signaling via an ERα-dependent mechanism in MCF-7 cells.

Keywords: Estrogen receptor, PI3K, PIP₃, 17β-estradiol

Notes

This paper was supported by research fund of Chonbuk National University 2003.

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