UCLA scientists find cell pathway driving a deadly sub-type of bre...( An intra cellular pathway not previo...),Health

An intra cellular pathway not previously linked to breast cancer is driving a sub-type of the disease that is highly lethal and disproportionately over-represented in African American women.

The pathway regulates how cells identify and destroy proteins and represents a class of genes called proteasome targeting complexes. The work shows that basal cancer cells degrade the tumor suppressor gene p27 by making a new type of proteasome targeting complex. The gene p27 is one of a handful of proteins that are expressed in normal cells and act to prevent rapid cell growth, which is indicative of cancer. Beyond chemotherapy, no specific therapeutic target has been identified for this sub-type of cancer, found in between 12 to 15 percent of breast cancers in the general population and up to 25 percent of cases in African American women.

"The mortality rates in this subgroup of cancer are very high," said Tim Lane, senior author of the paper and a researcher at UCLA's Jonsson Comprehensive Cancer Center. "The possibility that this new proteasome targeting complex might provide targets for therapeutic intervention is a completely new area for breast cancer research."

The research, done in animal models and human breast cancer cell lines, is published in the Nov. 15 issue of the journal Genes and Development.

Scientists have identified five to seven different sub-types of breast cancer. Basal-like breast cancers currently are among the most difficult to treat.

Targeted therapeutics are available for several sub-types. Women with HER-2 positive breast cancers can receive Herceptin, which when paired with chemotherapy extends disease-free survival by more than 50 percent. HER-2 positive women used to have the worst prognoses before Herceptin was developed. They now have the best prognoses because the drug targets what's broken in the cancer cell that is driving the disease. Another sub-type includes women with Estrogen
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