FRIDAY, Feb. 27 (HealthDay News) -- Switching on the estrogen receptor (ER) gene in the one-third of breast cancers that do not produce the receptor, which have a poor prognosis, restores their sensitivity to tamoxifen, according to the results of a study published online Feb. 23 in the Proceedings of the National Academy of Sciences Early Edition.
Caroline E. Ford, Ph.D., and colleagues from Malmo University Hospital in Malmo, Sweden, investigated the reported association between ERα loss and loss of Wnt-5a signaling in breast cancer cells.
The investigators found that stimulating Wnt-5a signaling with its ligand or a small peptide restored expression of ERα, which was accompanied by modifications of the ERα gene. This rendered the cells sensitive to the selective ERα modulator tamoxifen, as assessed by induction of cell death and inhibition of cell growth, the researchers report. Activating Wnt-5a signaling also increased ERα levels in a mouse model of ER-negative, metastatic breast cancer, the report indicates.
"This represents the first evidence that Wnt-5a signaling acts to re-establish ERα expression in ERα-negative breast cancer cells," Ford and colleagues conclude. "This novel approach of reconstituting ERα expression by using a natural cell surface receptor ligand, or a hexapeptide mimicking this ligand, to render tumors responsive to current endocrine treatments could be of significant importance to future clinical management of breast cancer."
Ford and a study co-author have filed a patent for the effects of the hexapeptide (Foxy-5) on the estrogen receptor.
Abstract
Full Text (subscription or payment may be required)
