PMID- 16169518
OWN - NLM
STAT- MEDLINE
DCOM- 20051212
LR  - 20230718
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 336
IP  - 4
DP  - 2005 Nov 4
TI  - 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.
PG  - 1221-6
AB  - 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.
FAU - Lee, Young-Rae
AU  - Lee YR
AD  - Department of Biochemistry, Center for Healthcare Technology Development, Chonbuk 
      National University Medical School, Jeonju, Republic of Korea.
FAU - Park, Jinny
AU  - Park J
FAU - Yu, Hong-Nu
AU  - Yu HN
FAU - Kim, Jong-Suk
AU  - Kim JS
FAU - Youn, Hyun Jo
AU  - Youn HJ
FAU - Jung, Sung Hoo
AU  - Jung SH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Phosphatidylinositol Phosphates)
RN  - 0 (phosphatidylinositol 3,4,5-triphosphate)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Breast Neoplasms/metabolism/*pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Estradiol/pharmacology/*physiology
MH  - Estrogen Receptor alpha/*agonists
MH  - Estrogen Receptor beta/*agonists
MH  - Female
MH  - Humans
MH  - Mammary Glands, Human/metabolism/pathology
MH  - Phosphatidylinositol 3-Kinases/biosynthesis/*physiology
MH  - Phosphatidylinositol Phosphates/metabolism
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/biosynthesis/*physiology
MH  - Signal Transduction
MH  - Up-Regulation
EDAT- 2005/09/20 09:00
MHDA- 2005/12/15 09:00
CRDT- 2005/09/20 09:00
PHST- 2005/08/25 00:00 [received]
PHST- 2005/08/28 00:00 [accepted]
PHST- 2005/09/20 09:00 [pubmed]
PHST- 2005/12/15 09:00 [medline]
PHST- 2005/09/20 09:00 [entrez]
AID - S0006-291X(05)01972-8 [pii]
AID - 10.1016/j.bbrc.2005.08.256 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2005 Nov 4;336(4):1221-6. doi: 
      10.1016/j.bbrc.2005.08.256.