RESEARCHERS able to genetically alter mice resistant to common breast cancers

Wednesday, June 27th 2001, 12:00 am

By: News On 6

Scientists have genetically engineered mice that are immune to some of the most common types of breast cancer, a development they say brings science a step closer to creating drugs to precisely block the spread of breast cancer in humans.

The research involves a protein linked to half of all human breast cancers. The bioengineered mice lack that protein, which tumors need to grow.

Though it could take years to develop a drug therapy targeting the protein, the findings are dramatic proof that certain breast cancers can occur only when the protein is present, said Christopher Widnell, scientific program director of the Atlanta-based American Cancer Society.

``This work is taking us to the next phase, where you can actually start designing intelligent treatments for individual tumors,'' said Widnell, who wasn't involved in the research.

The Dana-Farber Cancer Institute researchers produced the cancer-resistant mice by building on earlier success in engineering mice that don't express the protein cyclin D1, one of many proteins that regulate cell growth.

They wanted to test whether eliminating the protein in mice prone to certain breast cancers could keep them cancer-free.

The researchers bred the mice engineered to not express cyclin D1 with four other types of laboratory mice, each prone to different types of breast cancer, and monitored their offspring for signs of cancer. Two of the resulting cross-breeds were immune to the type of breast cancer for which they carried a gene.

Piotr Sicinski, a Dana-Farber researcher, said the findings clearly show two cancer genes called Neu and Ras can only turn normal cells into cancer cells by sending signals through the cyclin D1 protein.

The fact the mice with the two other cancer genes, called Wnt-1 and Myc, developed breast cancers means those cancer genes are capable of signaling though other cell-regulating proteins, Sicinski said.

The research appears in Thursday's issue of the journal Nature.

Sicinski said he and his colleagues want to see other researchers try to target cyclin D1 using existing cancer-blocking drugs.

He suggested pairing drugs that target a protein partner of the cell-regulating proteins that include cyclin D1 with Genentech's breast cancer drug, Herceptin, which aims to block the Neu cancer gene. That cancer gene has been linked to about 30 percent of human breast cancers.

``If you had a way to take out cyclin D1 you could completely unplug the (cancer gene) pathways from the cell cycle machinery without compromising the patient's health,'' Sicinski said.

In an accompanying Nature commentary, two Danish scientists said that when more is known about the cellular changes that the Neu and Ras cancer genes induce through cyclin D1, physicians might be able to create molecular profiles of breast cancer patients to target their unique mix of tumors.

``It might one day be possible to provide tailor-made treatments,'' say Jiri Bartek and Jiri Lukas of the Institute of Cancer Biology, Danish Cancer Society, Copenhagen.