A University of Michigan study, led by Elizabeth Petty, M.D., a professor in the departments of human genetics and internal medicine, determined that CHFR expression is missing in more than one-third of breast cancers. Breast cells produce new cells that are predisposed to become cancerous unless they receive the protective action of the CHFR gene.
The new study reveals how and why new “daughter” cells, produced as cells in body tissues renew themselves, receive too few or too many chromosomes if expression of the CHFR gene is missing or low.
“Our findings show that loss of CHFR disrupts normal chromosome segregation in breast cells during cell division and creates genomic instability, which can drive genetic mechanisms that accelerate the development of cancer,” says Dr. Petty
Previous research has shown that cancer cells that have low or absent CHFR expression are more susceptible to treatment with taxanes that attack the dividing cells when they are trying to separate their chromosomes.
Why do some women lack CHFR function or have low function in the first place? Dr. Petty says that there’s no evidence that women inherit mutations that lead to low or absent CHFR protein, but rather some other mechanism is shutting down the CHFR gene.
“We are actively looking at ways in which CHFR may be turned off in normal cells, in hopes that we can find a molecular switch to keep it turned on and decrease the risk of cancer development.”
Dr. Petty and her team studied normal and cancerous human breast tissue samples in cell culture to find out how CHFR affects certain proteins. They focused on proteins that regulate how spindles form and how chromosomes divide and form along the spindle. The team found that CHFR interacts with alpha tubulin, a protein important in forming mitotic spindles, and with a key mitotic spindle checkpoint regulator, MAD2, previously implicated in breast cancer. They found that when CHFR is absent, MAD2 does not do its job.
“Cells without CHFR not only have problems creating the structure or apparatus necessary to separate the chromosomes between the two daughter cells during cell division. They also have an impaired ability to detect and correct the problem before the chromosomes separate,” says Petty. “Prior to our findings, we knew that breast cancer cells often had the wrong number of chromosomes, but no one had identified any gene, or group of genes, that could account for the high frequency of this problem.”
“The new study,” the authors say, “provides one reason why the majority of breast cancer cells have too many chromosomes, which is a major hallmark of malignant cancer.”
The article appears online ahead of print in the journal Neoplasia.
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