Scientists from the Florida campus of The Scripps Research Institute
(TSRI) have identified a novel synthetic compound that sharply inhibits
the activity of a protein that plays an important role in in the
progression of breast and pancreatic cancers.
In the new study, to be published in the February 2015 print edition of the journal Molecular Pharmacology,
the scientists showed that the compound, known as SR1848, reduces the
activity and expression of the cancer-related protein called “liver
receptor homolog-1” or LRH-1.
“Our study shows that SR1848 removes LRH1 from DNA, shutting down
expression of LRH-1 target genes, and halts cell proliferation,” said
Patrick Griffin, chair of the (TSRI) Department of Molecular Therapeutics
and director of the Translational Research Institute at Scripps Florida.
“It’s a compound that appears to be a promising chemical scaffold for
fighting tumors that are non-responsive to standard therapies.”
LRH1 plays a crucial role in breast cancer through its regulation of
genes involved in hormone synthesis and cholesterol metabolism, also key
risk factors in cardiovascular disease. LRH-1 has also been implicated
as a tumor promoter in intestinal and pancreatic cancer. Over-expression
of LRH-1 has been shown to promote evasiveness and metastasis, the
usually lethal spread of the disease.
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