PMID- 17030631
OWN - NLM
STAT- MEDLINE
DCOM- 20070124
LR  - 20181113
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 26
IP  - 24
DP  - 2006 Dec
TI  - Mammary tumorigenesis and metastasis caused by overexpression of insulin receptor 
      substrate 1 (IRS-1) or IRS-2.
PG  - 9302-14
AB  - Insulin receptor substrates (IRSs) are signaling adaptors that play a major role 
      in the metabolic and mitogenic actions of insulin and insulin-like growth 
      factors. Reports have recently noted increased levels, or activity, of IRSs in 
      many human cancers, and some have linked this to poor patient prognosis. We found 
      that overexpressed IRS-1 was constitutively phosphorylated in vitro and in vivo 
      and that transgenic mice overexpressing IRS-1 or IRS-2 in the mammary gland 
      showed progressive mammary hyperplasia, tumorigenesis, and metastasis. Tumors 
      showed extensive squamous differentiation, a phenotype commonly seen with 
      activation of the canonical beta-catenin signaling pathway. Consistent with this, 
      IRSs were found to bind beta-catenin in vitro and in vivo. IRS-induced 
      tumorigenesis is unique, given that the IRSs are signaling adaptors with no 
      intrinsic kinase activity, and this supports a growing literature indicating a 
      role for IRSs in cancer. This study defines IRSs as oncogene proteins in vivo and 
      provides new models to develop inhibitors against IRSs for anticancer therapy.
FAU - Dearth, Robert K
AU  - Dearth RK
AD  - Breast Cancer, Baylor College of Medicine and Methodist Hospital, Department of 
      Medicine, Houston, TX 77030, USA.
FAU - Cui, Xiaojiang
AU  - Cui X
FAU - Kim, Hyun-Jung
AU  - Kim HJ
FAU - Kuiatse, Isere
AU  - Kuiatse I
FAU - Lawrence, Nicole A
AU  - Lawrence NA
FAU - Zhang, Xiaomei
AU  - Zhang X
FAU - Divisova, Jana
AU  - Divisova J
FAU - Britton, Ora L
AU  - Britton OL
FAU - Mohsin, Syed
AU  - Mohsin S
FAU - Allred, D Craig
AU  - Allred DC
FAU - Hadsell, Darryl L
AU  - Hadsell DL
FAU - Lee, Adrian V
AU  - Lee AV
LA  - eng
GR  - R01DK52197/DK/NIDDK NIH HHS/United States
GR  - T32 CA090221/CA/NCI NIH HHS/United States
GR  - P01CA30195/CA/NCI NIH HHS/United States
GR  - T32 DK007696/DK/NIDDK NIH HHS/United States
GR  - P01 CA030195/CA/NCI NIH HHS/United States
GR  - DK07696/DK/NIDDK NIH HHS/United States
GR  - R01 DK052197/DK/NIDDK NIH HHS/United States
GR  - CA90221/CA/NCI NIH HHS/United States
GR  - R01 CA094118/CA/NCI NIH HHS/United States
GR  - R01CA94118/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20061009
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Adaptor Proteins, Signal Transducing)
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)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/biosynthesis/genetics
MH  - Animals
MH  - Cell Line, Transformed
MH  - Female
MH  - Humans
MH  - Hyperplasia
MH  - Insulin Receptor Substrate Proteins
MH  - Intracellular Signaling Peptides and Proteins/*genetics/physiology
MH  - Lung Neoplasms/genetics/pathology/*secondary
MH  - Mammary Glands, Animal/pathology
MH  - Mammary Neoplasms, Experimental/*genetics/pathology
MH  - Mice
MH  - Mice, Transgenic
MH  - Neoplasm Metastasis/genetics/pathology
MH  - Phosphoproteins/*biosynthesis/*genetics/physiology
MH  - Signal Transduction/physiology
PMC - PMC1698542
EDAT- 2006/10/13 09:00
MHDA- 2007/01/25 09:00
PMCR- 2007/04/01
CRDT- 2006/10/13 09:00
PHST- 2006/10/13 09:00 [pubmed]
PHST- 2007/01/25 09:00 [medline]
PHST- 2006/10/13 09:00 [entrez]
PHST- 2007/04/01 00:00 [pmc-release]
AID - MCB.00260-06 [pii]
AID - 0260-06 [pii]
AID - 10.1128/MCB.00260-06 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2006 Dec;26(24):9302-14. doi: 10.1128/MCB.00260-06. Epub 2006 Oct 
      9.