New Gene May Intensify Breast Cancer Growth
BETHESDA, Md. - Scientists in the National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) have discovered a new gene that is pivotal to a crucial metabolic pathway linked to the growth and progression of human breast cancer. The gene appears to be expressed at abnormally high levels in tumor cells of most breast cancer patients, more than half of cases examined so far. The researchers reported their findings in the August 15 issue of Science.
In many cancers, but especially breast cancer, tumor cells accumulate extra copies of genes that give the cancer a growth advantage. The new gene is one such amplified gene. The gene, previously unknown, is linked to the estrogen response pathway. The scientists expect further study of the gene to help reveal the basic biology of tumor cells, especially those responsive to steroid hormones. This group of diseases includes not just breast and ovarian cancer, but prostate cancer as well.
The NHGRI researchers found the gene, which they call AIB1 (amplified in breast cancer-1), by searching the long arm of chromosome 20 for genes whose expression and copy number are elevated in breast cancer. The gene is expressed at lower levels in normal human tissue. AIB1 is the most recently identified member of a gene family known as SRC-1 (steroid receptor coactivator), all of which interact with genes for steroid hormone receptors, ultimately enhancing tumor cell growth.
"Its another example where information that we have about other members of this gene family allows us to infer that this may be very important in breast biology, regulating not just steroid growth response but possibly other growth response pathways. It could eventually be a target for therapeutics. It will certainly be a target for significant additional biologic studies to understand its action," said Dr. Paul Meltzer, the senior author of the paper, and a faculty member of the NHGRIs Division of Intramural Research, at the NIH.
The finding is too new to have an immediate impact on breast cancer therapies. "At this early stage, were really thinking more in terms of the fundamental cell biology of breast cancer. We think this gene is probably part of the engine that drives the growth of some breast cancers, and we're trying to understand how that works," said Dr. Jeffrey Trent, a co-author of the paper and head of the NHGRI laboratory where the gene was cloned.
The researchers have also begun to design the first clinical studies using the gene as a marker to find out how it affects the course of breast cancer. "Do the patients who make a lot of the message from this gene respond differently to therapy, do they have a different clinical outcome, are their tumors different, do they develop at a different age or at a different rate? We don't have answers to any of those questions yet, but we are actively seeking the answers," said Trent.
"A lot is known about how steroid receptors work, but the wiring of how they send their signals has been imperfectly understood. There are a lot of different genes which seem to be part of this system. We suspect that this one is a particularly important part of the wiring system in the breast cancer cell that transmits the signal from steroids like estrogen that says grow," Meltzer said. "It gives us an important new window into the cell biology of breast cancer that emphasizes the importance of this particular kind of gene to the growth of cancer cells in a significant number of patients. And that's going to be an extremely interesting thing to investigate."
Previously, other genes found to be amplified in breast cancer have led to clinical tests and trials of therapy. AIB1 may turn out to be a new candidate for similar development, Meltzer noted.
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Last Reviewed: September 2006