Pattern appears to be regulated by a single antitumor gene, according to PNAS study.
Researchers identified a pattern of gene activity in mice that may help predict individual risk for breast cancer metastasis and survival. They also found that a single gene, bromodomain 4 (Brd4), regulates the expression of this profile.
The investigators engineered highly metastatic mouse mammary tumor cells that expressed Brd4. They found that Brd4-expressing cells were less invasive and less mobile than non-Brd4-expressing cells yet showed no change in their rate of growth.
They then implanted their metastatic Brd4-expressing cells into mice. After four weeks, the researchers found that Brd4-expressing metastatic cells seemed to suppress both tumor growth and metastasis. The mice had dramatically smaller tumors and fewer metastatic tumors in their lungs compared to control-group mice.
The researchers then examined human gene signatures identified from microarray data from the NCBI Gene Expression Omnibus and Rosetta Informatics. The team identified a set of 379 genes in humans that are similar to the genes affected by Brd4 expression in the mouse model. They found that the level of activation of Brd4 or Brd4-associated pathways within a tumor were an important determinant of relapse and survival. Brd4 seemed to drive the expression of many genes present in the signature.
Using the Brd4 gene signature, the researchers were able to predict survival and relapse of breast cancer patients in five separate datasets. They were also able to predict the survival of subsets of patients whose breast cancer had not spread to their lymph nodes and patients with estrogen-receptor positive tumors.
The research was a collaborative effort between the NCI and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The findings appeared in the April 21 online issue of the Proceedings of the National Academy of Sciences.
