Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:O76050 (
neu
)
3,969
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The Rac-GEF,
P-Rex1
, activates Rac1 signaling downstream of G protein-coupled receptors and PI3K. Increased
P-Rex1
expression promotes melanoma progression; however, its role in breast cancer is complex, with differing reports of the effect of its expression on disease outcome. To address this we analyzed human databases, undertook gene array expression analysis, and generated unique murine models of
P-Rex1
gain or loss of function. Analysis of
PREX1
mRNA expression in breast cancer cDNA arrays and a METABRIC cohort revealed that higher
PREX1
mRNA in ER
+ve
/luminal tumors was associated with poor outcome in luminal B cancers.
Prex1
deletion in MMTV-
neu
or MMTV-
PyMT
mice reduced Rac1 activation in vivo and improved survival. High level MMTV
-
driven transgenic
PREX1
expression resulted in apicobasal polarity defects and increased mammary epithelial cell proliferation associated with hyperplasia and development of de novo mammary tumors. MMTV-
PREX1
expression in MMTV-
neu
mice increased tumor initiation and enhanced metastasis in vivo, but had no effect on primary tumor growth. Pharmacological inhibition of Rac1 or MEK1/2 reduced
P-Rex1
-driven tumoroid formation and cell invasion. Therefore,
P-Rex1
can act as an oncogene and cooperate with HER2/
neu
to enhance breast cancer initiation and metastasis, despite having no effect on primary tumor growth.
...
PMID:PtdIns(3,4,5)P
3
-dependent Rac exchanger 1 (P-Rex1) promotes mammary tumor initiation and metastasis. 3309 62
