PMID- 15528270
OWN - NLM
STAT- MEDLINE
DCOM- 20050628
LR  - 20210727
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 19
IP  - 3
DP  - 2005 Mar
TI  - The Src kinase pathway promotes tamoxifen agonist action in Ishikawa endometrial 
      cells through phosphorylation-dependent stabilization of estrogen receptor 
      (alpha) promoter interaction and elevated steroid receptor coactivator 1 
      activity.
PG  - 732-48
AB  - Tamoxifen is the most widely used selective estrogen receptor modulator for 
      breast cancer in clinical use today. However, tamoxifen agonist action in 
      endometrium remains a major hurdle for tamoxifen therapy. Activation of the 
      nonreceptor tyrosine kinase src promotes tamoxifen agonist action, although the 
      mechanisms remain unclear. To examine these mechanisms, the effect of src kinase 
      on estrogen and tamoxifen signaling in tamoxifen-resistant Ishikawa endometrial 
      adenocarcinoma cells was assessed. A novel connection was identified between src 
      kinase and serine 167 phosphorylation in estrogen receptor (ER)-alpha via 
      activation of AKT kinase. Serine 167 phosphorylation stabilized ER interaction 
      with endogenous ER-dependent promoters. Src kinase exhibited the additional 
      function of potentiating the transcriptional activity of Gal-steroid receptor 
      coactivator 1 (SRC-1) and Gal-cAMP response element binding protein-binding 
      protein in endometrial cancer cells while having no effect on Gal-p300-associated 
      factor and Gal fusions of the other p160 coactivators glucocorticoid-interacting 
      protein 1 (transcriptional intermediary factor 2/nuclear coactivator-2/SRC-2) and 
      amplified in breast cancer 1 (receptor-associated coactivator 3/activator of 
      transcription of nuclear receptor/SRC-3). Src effects on ER phosphorylation and 
      SRC-1 activity both contributed to tamoxifen agonist action on ER-dependent gene 
      expression in Ishikawa cells. Taken together, these data demonstrate that src 
      kinase potentiates tamoxifen agonist action through serine 167-dependent 
      stabilization of ER promoter interaction and through elevation of SRC-1 and cAMP 
      response element binding protein-binding protein coactivation of ER.
FAU - Shah, Yatrik M
AU  - Shah YM
AD  - Department of Biochemistry and Molecular Biology, Medical College of Ohio, 3035 
      Arlington Ave., Toledo, Ohio 43614-5804, USA.
FAU - Rowan, Brian G
AU  - Rowan BG
LA  - eng
GR  - R01 DK06832/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20041104
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Antineoplastic Agents, Hormonal)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Transcription Factors)
RN  - 094ZI81Y45 (Tamoxifen)
RN  - 17197F0KYM (afimoxifene)
RN  - 452VLY9402 (Serine)
RN  - 4TI98Z838E (Estradiol)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (NCOA1 protein, human)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.2 (src-Family Kinases)
SB  - IM
MH  - Antineoplastic Agents, Hormonal/pharmacology
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Chromatin Immunoprecipitation
MH  - Cyclic AMP/metabolism
MH  - Endometrial Neoplasms/*drug therapy/pathology
MH  - Estradiol/pharmacology
MH  - Female
MH  - Genes, Dominant
MH  - Genes, Reporter
MH  - HeLa Cells
MH  - Histone Acetyltransferases
MH  - Humans
MH  - Luciferases/metabolism
MH  - Models, Biological
MH  - Nuclear Receptor Coactivator 1
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation
MH  - Plasmids/metabolism
MH  - Promoter Regions, Genetic
MH  - RNA, Small Interfering/metabolism
MH  - Receptors, Estrogen/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Serine/chemistry
MH  - Tamoxifen/*agonists/*analogs & derivatives/*pharmacology
MH  - Time Factors
MH  - Transcription Factors/metabolism
MH  - Transcription, Genetic
MH  - src-Family Kinases/*metabolism
EDAT- 2004/11/06 09:00
MHDA- 2005/06/29 09:00
CRDT- 2004/11/06 09:00
PHST- 2004/11/06 09:00 [pubmed]
PHST- 2005/06/29 09:00 [medline]
PHST- 2004/11/06 09:00 [entrez]
AID - me.2004-0298 [pii]
AID - 10.1210/me.2004-0298 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2005 Mar;19(3):732-48. doi: 10.1210/me.2004-0298. Epub 2004 Nov 
      4.