PMID- 10319328
OWN - NLM
STAT- MEDLINE
DCOM- 19990708
LR  - 20181201
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 13
IP  - 5
DP  - 1999 May
TI  - Enhancement of insulin-like growth factor signaling in human breast cancer:
      estrogen regulation of insulin receptor substrate-1 expression in vitro and in
      vivo.
PG  - 787-96
AB  - Cross-talk between insulin-like growth factor (IGF)- and estrogen receptor
      (ER)-signaling pathways results in synergistic growth. We show here that estrogen
      enhances IGF signaling by inducing expression of three key IGF-regulatory
      molecules, the type 1 IGF receptor (IGFR1) and its downstream signaling
      molecules, insulin receptor substrate (IRS)-1 and IRS-2. Estrogen induction of
      IGFR1 and IRS expression resulted in enhanced tyrosine phosphorylation of IRS-1
      after IGF-I stimulation, followed by enhanced mitogen-activated protein kinase
      activation. To examine whether these pathways were similarly activated in vivo,
      we examined MCF-7 cells grown as xenografts in athymic mice. IRS-1 was expressed 
      at high levels in estrogen-dependent growth of MCF-7 xenografts, but withdrawal
      of estrogen, which decreased tumor growth, resulted in a dramatic decrease in
      IRS-1 expression. Finally, we have shown that high IRS-1 expression is an
      indicator of early disease recurrence in ER-positive human primary breast tumors.
      Taken together, these data not only reinforce the concept of cross-talk between
      IGF- and ER-signaling pathways, but indicate that IGF molecules may be critical
      regulators of estrogen-mediated growth and breast cancer pathogenesis.
FAU - Lee, A V
AU  - Lee AV
AD  - Department of Medicine, University of Texas Health Science Center at San Antonio 
      78284-7884, USA. adrian@oncology.uthscsa.edu
FAU - Jackson, J G
AU  - Jackson JG
FAU - Gooch, J L
AU  - Gooch JL
FAU - Hilsenbeck, S G
AU  - Hilsenbeck SG
FAU - Coronado-Heinsohn, E
AU  - Coronado-Heinsohn E
FAU - Osborne, C K
AU  - Osborne CK
FAU - Yee, D
AU  - Yee D
LA  - eng
GR  - P01CA-30195/CA/NCI NIH HHS/United States
GR  - P30CA-54174/CA/NCI NIH HHS/United States
GR  - P50CA-58183-06/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Estrogen Antagonists)
RN  - 0 (Estrogens)
RN  - 0 (IRS1 protein, human)
RN  - 0 (IRS2 protein, human)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Irs1 protein, mouse)
RN  - 0 (Irs2 protein, mouse)
RN  - 0 (Phosphoproteins)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Receptors, Somatomedin)
RN  - 0 (Somatomedins)
RN  - 22X328QOC4 (Fulvestrant)
RN  - 4TI98Z838E (Estradiol)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.10.1 (Receptor, Insulin)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
SB  - IM
MH  - Animals
MH  - Breast Neoplasms/drug therapy/*metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinases/drug effects/metabolism
MH  - Estradiol/analogs & derivatives/pharmacology
MH  - Estrogen Antagonists/pharmacology
MH  - Estrogens/*metabolism
MH  - Female
MH  - Fulvestrant
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Insulin Receptor Substrate Proteins
MH  - Insulin-Like Growth Factor I/metabolism/pharmacology
MH  - Intracellular Signaling Peptides and Proteins
MH  - Mammary Neoplasms, Experimental/metabolism
MH  - Mice
MH  - Phosphoproteins/genetics/*metabolism
MH  - Phosphorylation
MH  - Receptor, Insulin/genetics/metabolism
MH  - Receptors, Estrogen/metabolism
MH  - Receptors, Somatomedin/genetics/metabolism
MH  - Signal Transduction
MH  - Somatomedins/*metabolism
MH  - Survival Rate
MH  - Transplantation, Heterologous
MH  - Tumor Cells, Cultured
EDAT- 1999/05/13 00:00
MHDA- 1999/05/13 00:01
CRDT- 1999/05/13 00:00
PHST- 1999/05/13 00:00 [pubmed]
PHST- 1999/05/13 00:01 [medline]
PHST- 1999/05/13 00:00 [entrez]
AID - 10.1210/mend.13.5.0274 [doi]
PST - ppublish
SO  - Mol Endocrinol. 1999 May;13(5):787-96. doi: 10.1210/mend.13.5.0274.