Mutations of BRCA1 have long been recognized as a cancer stimulant. About five to 10% of breast cancer cases are linked to genetic miscues, half of which are linked to the gene.
In a new paper published in the August 1 issue of Cancer Research, cyclin D1, a protein overproduced in about half of all cases of breast cancer, has been shown to disrupt BRCA1’s normal role as a cancer inhibitor. As such, the results reaffirm the protein as a candidate target for molecular therapeutic control of breast tumor development.
“Cyclin D1 is a collaborative oncogene and is sufficient for the induction of breast tumorogenesis in transgenic mice,” he said. “This protein blocks the functional activity of the BRCA1 tumor suppressor.”
Cyclin D1 interferes with BRCA1 function because the two proteins both bind to the same spot on ER alpha, a protein that governs cell proliferation properties in both healthy and cancerous cells. In healthy cells, BRCA1 binds to ER alpha to restrain and control estrogen-target genes that promote cell division. In cancer cells, however, cyclin D1 occupies the binding site on the ER alpha to promote proliferation. The abundance of cyclin D1 pre-empts BRCA1 binding to the estrogen receptor and negates the tumor suppressor role of the BRCA1 gene product.