PMID- 23825155
OWN - NLM
STAT- MEDLINE
DCOM- 20140409
LR  - 20211021
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 34
IP  - 12
DP  - 2013 Dec
TI  - Expression of a phosphorylated substrate domain of p130Cas promotes PyMT-induced 
      c-Src-dependent murine breast cancer progression.
PG  - 2880-90
LID - 10.1093/carcin/bgt238 [doi]
AB  - Elevated expression of p130Cas (Crk-associated substrate)/BCAR1 (breast cancer 
      antiestrogen resistance 1) in human breast tumors is a marker of poor prognosis 
      and poor overall survival. p130Cas is a downstream target of the tyrosine kinase 
      c-Src. Signaling mediated by p130Cas through its phosphorylated substrate domain 
      (SD) and interaction with effector molecules directly promotes tumor progression. 
      We previously developed a constitutively phosphorylated p130Cas SD molecule, 
      Src*/SD (formerly referred to as Src*/CasSD), which acts as decoy molecule and 
      attenuates the transformed phenotype in v-crk-transformed murine fibroblasts and 
      human breast cancer cells. To test the function of this molecule in vivo, we 
      established mouse mammary tumor virus (MMTV)-long terminal repeat-Src*/SD 
      transgenic mice in which mammary gland development and tumor formation were 
      analyzed. Transgenic expression of the Src*/SD molecule under the MMTV-long 
      terminal repeat promoter did not interfere with normal mammary gland development 
      or induce tumors in mice observed for up to 11 months. To evaluate the effects of 
      the Src*/SD molecule on tumor development in vivo, we utilized the MMTV-polyoma 
      middle T-antigen (PyMT) murine breast cancer model that depends on c-Src. PyMT 
      mice crossed with Src*/SD mice displayed accelerated tumor formation. The earlier 
      onset of tumors can be explained by the interaction of the Src* domain with PyMT 
      and targeting the fused phosphorylated SD to the membrane. At membrane 
      compartments, it might integrate membrane-associated active signaling complexes 
      leading to increased proliferation measured by phospho-Histone H3 staining. 
      Although these results were unexpected, they emphasize the importance of 
      preventing the membrane association of Src*/SD when employed as decoy molecule.
FAU - Zhao, Yingshe
AU  - Zhao Y
AD  - Department of Biochemistry, Boston University School of Medicine, Boston, MA 
      02118, USA.
FAU - Kumbrink, Joerg
AU  - Kumbrink J
FAU - Lin, Bor-Tyh
AU  - Lin BT
FAU - Bouton, Amy H
AU  - Bouton AH
FAU - Yang, Shi
AU  - Yang S
FAU - Toselli, Paul A
AU  - Toselli PA
FAU - Kirsch, Kathrin H
AU  - Kirsch KH
LA  - eng
GR  - R01 CA143108/CA/NCI NIH HHS/United States
GR  - CA143108/CA/NCI NIH HHS/United States
GR  - CA096846/CA/NCI NIH HHS/United States
GR  - CA106468/CA/NCI 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.
DEP - 20130703
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (Crk-Associated Substrate Protein)
SB  - IM
MH  - Animals
MH  - Breast Neoplasms/*genetics/metabolism/*pathology
MH  - Carcinogenesis/genetics/pathology
MH  - Crk-Associated Substrate Protein/*genetics/metabolism
MH  - Disease Progression
MH  - Female
MH  - Fibroblasts/metabolism/pathology
MH  - Genes, src/*genetics
MH  - Mammary Glands, Animal/metabolism/pathology
MH  - Mammary Neoplasms, Experimental/genetics/metabolism/pathology
MH  - Mammary Tumor Virus, Mouse/genetics/metabolism
MH  - Mice
MH  - Mice, Transgenic/genetics/metabolism
MH  - Phosphorylation/*genetics
MH  - Rats
PMC - PMC3845889
EDAT- 2013/07/05 06:00
MHDA- 2014/04/10 06:00
PMCR- 2014/12/01
CRDT- 2013/07/05 06:00
PHST- 2013/07/05 06:00 [entrez]
PHST- 2013/07/05 06:00 [pubmed]
PHST- 2014/04/10 06:00 [medline]
PHST- 2014/12/01 00:00 [pmc-release]
AID - bgt238 [pii]
AID - 10.1093/carcin/bgt238 [doi]
PST - ppublish
SO  - Carcinogenesis. 2013 Dec;34(12):2880-90. doi: 10.1093/carcin/bgt238. Epub 2013 
      Jul 3.