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Up-regulation of PI3K/Akt signaling by 17beta-estradiol through activation of estrogen receptor-alpha, but not estrogen receptor-beta, and stimulates cell growth in breast cancer cells.
Biochem Biophys Res Commun. 2005 Nov 04; 336(4):1221-6.BB

Abstract

Estrogen stimulates cell proliferation in breast cancer. The biological effects of estrogen are mediated through two intracellular receptors, estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta). However, the role of ERs in the proliferative action of estrogen is not well established. Recently, it has been known that ER activates phosphatidylinositol-3-OH kinase (PI3K) through binding with the p85 regulatory subunit of PI3K. Therefore, possible mechanisms may include ER-mediated phosphoinositide metabolism with subsequent formation of phosphatidylinositol-3,4,5-trisphosphate (PIP(3)), which is generated from phosphatidylinositol 4,5-bisphosphate via PI3K activation. The present study demonstrates that 17beta-estradiol (E2) up-regulates PI3K in an ERalpha-dependent manner, but not ERbeta, and stimulates cell growth in breast cancer cells. In order to study this phenomenon, we have treated ERalpha-positive MCF-7 cells and ERalpha-negative MDA-MB-231 cells with 10nM E2. Treatment of MCF-7 cells with E2 resulted in a marked increase in PI3K (p85) expression, which paralleled an increase in phospho-Akt (Ser-473) and PIP(3) level. These observations also correlated with an increased activity to E2-induced cell proliferation. However, these effects of E2 on breast cancer cells were not observed in the MDA-MB-231 cell line, indicating that the E2-mediated up-regulation of PI3K/Akt pathway is ERalpha-dependent. These results suggest that estrogen activates PI3K/Akt signaling through ERalpha-dependent mechanism in MCF-7 cells.

Authors+Show Affiliations

Department of Biochemistry, Center for Healthcare Technology Development, Chonbuk National University Medical School, Jeonju, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16169518

Citation

Lee, Young-Rae, et al. "Up-regulation of PI3K/Akt Signaling By 17beta-estradiol Through Activation of Estrogen Receptor-alpha, but Not Estrogen Receptor-beta, and Stimulates Cell Growth in Breast Cancer Cells." Biochemical and Biophysical Research Communications, vol. 336, no. 4, 2005, pp. 1221-6.
Lee YR, Park J, Yu HN, et al. Up-regulation of PI3K/Akt signaling by 17beta-estradiol through activation of estrogen receptor-alpha, but not estrogen receptor-beta, and stimulates cell growth in breast cancer cells. Biochem Biophys Res Commun. 2005;336(4):1221-6.
Lee, Y. R., Park, J., Yu, H. N., Kim, J. S., Youn, H. J., & Jung, S. H. (2005). Up-regulation of PI3K/Akt signaling by 17beta-estradiol through activation of estrogen receptor-alpha, but not estrogen receptor-beta, and stimulates cell growth in breast cancer cells. Biochemical and Biophysical Research Communications, 336(4), 1221-6.
Lee YR, et al. Up-regulation of PI3K/Akt Signaling By 17beta-estradiol Through Activation of Estrogen Receptor-alpha, but Not Estrogen Receptor-beta, and Stimulates Cell Growth in Breast Cancer Cells. Biochem Biophys Res Commun. 2005 Nov 4;336(4):1221-6. PubMed PMID: 16169518.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Up-regulation of PI3K/Akt signaling by 17beta-estradiol through activation of estrogen receptor-alpha, but not estrogen receptor-beta, and stimulates cell growth in breast cancer cells. AU - Lee,Young-Rae, AU - Park,Jinny, AU - Yu,Hong-Nu, AU - Kim,Jong-Suk, AU - Youn,Hyun Jo, AU - Jung,Sung Hoo, PY - 2005/08/25/received PY - 2005/08/28/accepted PY - 2005/9/20/pubmed PY - 2005/12/15/medline PY - 2005/9/20/entrez SP - 1221 EP - 6 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 336 IS - 4 N2 - Estrogen stimulates cell proliferation in breast cancer. The biological effects of estrogen are mediated through two intracellular receptors, estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta). However, the role of ERs in the proliferative action of estrogen is not well established. Recently, it has been known that ER activates phosphatidylinositol-3-OH kinase (PI3K) through binding with the p85 regulatory subunit of PI3K. Therefore, possible mechanisms may include ER-mediated phosphoinositide metabolism with subsequent formation of phosphatidylinositol-3,4,5-trisphosphate (PIP(3)), which is generated from phosphatidylinositol 4,5-bisphosphate via PI3K activation. The present study demonstrates that 17beta-estradiol (E2) up-regulates PI3K in an ERalpha-dependent manner, but not ERbeta, and stimulates cell growth in breast cancer cells. In order to study this phenomenon, we have treated ERalpha-positive MCF-7 cells and ERalpha-negative MDA-MB-231 cells with 10nM E2. Treatment of MCF-7 cells with E2 resulted in a marked increase in PI3K (p85) expression, which paralleled an increase in phospho-Akt (Ser-473) and PIP(3) level. These observations also correlated with an increased activity to E2-induced cell proliferation. However, these effects of E2 on breast cancer cells were not observed in the MDA-MB-231 cell line, indicating that the E2-mediated up-regulation of PI3K/Akt pathway is ERalpha-dependent. These results suggest that estrogen activates PI3K/Akt signaling through ERalpha-dependent mechanism in MCF-7 cells. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/16169518/Up_regulation_of_PI3K/Akt_signaling_by_17beta_estradiol_through_activation_of_estrogen_receptor_alpha_but_not_estrogen_receptor_beta_and_stimulates_cell_growth_in_breast_cancer_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(05)01972-8 DB - PRIME DP - Unbound Medicine ER -