Histone H1 Phosphorylation in Breast Cancer

Breast
cancer is the second leading cause of cancer-related deaths
in women. The need for new clinical biomarkers in breast cancer is
necessary to further predict prognosis and therapeutic response. In
this article, the LC-MS histone H1 phosphorylation profiles were established
for three distinct breast cancer cell lines. The results show that
the extent of H1 phosphorylation can distinguish between the different
cell lines. The histone H1 from the metastatic cell line, MDA-MB-231,
was subjected to chemical derivitization and LC-MS/MS analysis. The
results suggest that the phosphorylation at threonine 146 is found
on both histone H1.2 and histone H1.4. Cell lines were then treated
with an extracellular stimulus, estradiol or kinase inhibitor LY294002,
to monitor changes in histone H1 phosphorylation. The data show that
histone H1 phosphorylation can increase and decrease in response to
extracellular stimuli. Finally, primary breast tissues were stained
for the histone H1 phosphorylation at threonine 146. Variable staining
patterns across tumor grades and subtypes were observed with pT146
labeling correlating with tumor grade. These results establish the
potential for histone H1 phosphorylation at threonine 146 as a clinical
biomarker in breast cancer.