Link found between gene and 70% of ER-negative breast cancers

July 21, 2011

Researchers have identified a gene associated with 70% of estrogen receptor (ER)-negative breast cancers, reports a study published online July 14 in Nature.

Researchers have identified a gene associated with 70% of estrogen receptor (ER)-negative breast cancers, reports a study published online July 14 in Nature.

Investigators at Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, used a new technique-RNA interference (RNAi)-based loss-of-function screening-to analyze hundreds of genes at a time, seeking the ones that drive tumor formation and growth. When they injected cancerous cells with genetic material that can deactivate genes, they observed that the gene phosphoglycerate dehydrogenase (PHGDH) was significantly more active than normal in 70% of ER-negative tumors, which are difficult to treat because they don’t respond to hormone therapies.

The gene catalyzes production of the amino acid serine. Cancer cells with high PHGDH protein expression have increased serine synthesis; suppressing PHGDH markedly decreases cell proliferation and serine synthesis in cells with elevated PHGDH expression but not in cells without it.

The authors conclude that certain breast cancers depend on PHGDH overexpression to increase serine pathway flux. They assert that their findings demonstrate the usefulness of in vivo negative-selection RNAi screens to identify other potential anticancer targets.