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: EC:2.1.1.148 (
Thy1
)
1,210
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The surface glycoprotein THY is a marker of myoepithelial precursor cells, which are basal cells with epithelial-mesenchymal intermediate phenotype originating from the ectoderm. Myoepithelial precursor cells are lost during progression from
in situ
to invasive carcinoma. To define the functional role of
Thy1
-positive cells within the myoepithelial population, we tracked
Thy1
expression in human breast cancer samples, isolated THY1-positive myoepithelial progenitor cells (CD44
+
/CD24
low
/CD90
+
), and established long-term cultures (parental cells). Parental cells were used to generate a xenograft model to examine
Thy1
expression during tumor formation. Post-transplantation cell cultures lost
THY
1 expression through methylation at the
THY1
locus and this is associated with an increase in
EGFR
and
NOTCH1
transcript levels.
Thy1
-low cells are sensitive to the EGFR/HER2 dual inhibitor lapatinib. High
THY1
expression is associated with poorer relapse-free survival in patients with breast cancer.
THY1
methylation may track the shift of bipotent progenitors into differentiated cells.
Thy1
is a good candidate biomarker in basal-like breast cancer. IMPLICATIONS: Our findings provide evidence that
THY1
expression is lost in xenografts due to promoter methylation.
Thy1
-low cells with increased EGFR and Notch1 expression are responsive to target therapy. Because DNA methylation is often altered in early cancer development, candidate methylation markers may be exploited as biomarkers for basal-like breast cancer.
...
PMID:Epigenetic Silencing of
THY1
Tracks the Acquisition of the Notch1-EGFR Signaling in a Xenograft Model of CD44
+
/CD24
low
/CD90
+
Myoepithelial Cells. 3024 55
