Study links breast cancer gene to cell-cycle control

St. Jude Children's Research Hospital (ALSAC)
Tuesday, 15 May 2001

(Memphis, Tennessee, May 15, 2001) Scientists studying links between genetic mutations and breast cancer have confirmed a protein's role in halting replication of abnormal DNA at cell-cycle checkpoints.

Research at St. Jude Children's Research Hospital shows the Brca1 protein helps stop cell growth when alerted to DNA damaged by ionizing irradiation (IR). The study, authored by Michael B. Kastan, M.D., Ph.D., St. Jude hematology-oncology department chairman, is published in the May issue of Molecular and Cellular Biology.

Unchecked, this DNA damage may contribute to cancer development. Mutations in Brca1 are the most common cause of hereditary breast cancer.

The study indicates the Brca1 protein monitors cell-cycle checkpoints at both the DNA replication (S-phase) and mitosis, or cell division, (G2/M) stages. By alerting the cell to the presence of DNA damage, the role of Brca1 in arresting the cell cycle should help reduce the appearance of genetic mutations in the cells as they divide. Therefore, if a cell carries a mutated Brca1 gene, it would not properly function and would allow the damaged DNA to replicate or the damaged chromosomes to be segregated.

"Failure to stop the cell cycle after DNA damage could contribute to genetic changes that lead to cancer development," Kastan said. "We show that this protein is important at two distinct stages of the cell cycle. These results provide new insights into how breast cancer may develop when women inherit mutations in the Brca1 gene."

The researchers confirmed the protein's role in both DNA replication and mitosis checkpoints by studying breast cancer cells containing mutated Brca1 genes. When normal Brca1 was reintroduced into these cells, normal cell-cycle control was restored.

"This shows Brca1's role for the first time in the radiation-induced S-phase checkpoint and confirms its participation in the radiation-induced G2/M checkpoint," Kastan said. "This will lead to further understanding of the cell cycle and its links to cancer."

This research study was funded by a grant from the National Institutes of Health.

St. Jude Children's Research Hospital, in Memphis, Tenn., was founded by the late entertainer Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for catastrophic diseases of childhood. The hospital's work is supported by the American Lebanese Syrian Associated Charities® (ALSAC®). All St. Jude patients are treated regardless of their families' ability to pay. ALSAC covers all costs of treatment beyond those covered by third-party insurers and total costs for families who have no insurance.

For more information, or to contact St. Jude Children's Research Hospital (ALSAC), see their website at: www.stjude.org