Discovery May Lead to Cancer Test : Health: Researchers pinpoint protein that could help doctors more quickly determine whether breast disease has spread to other parts of the body.
In a discovery that could refine breast cancer treatment and spur new possibilities in the search for a cure, researchers have pinpointed a wayward protein that appears to play an important role in the disease.
Moreover, the gene that produces the protein is the same gene recently found responsible for many cases of hereditary breast cancer. “It suggests to us that this protein might be involved in a lot of cancers, instead of just the rare familial breast cancers, “ said Nancy Davidson, director of the breast cancer program at the Johns Hopkins Oncology Center in Baltimore.
The advance could lead--perhaps in just two or three years--to a test telling whether the cancer has spread to other parts of the body, said researchers at the University of Texas at San Antonio.
“That would be tremendously useful,” said Wen-Hwa Lee, director of the university’s Center for Molecular Medicine and head of the research team. “If we can elucidate how this protein functions inside the cell, we will be able to devise several tools to battle breast cancer in general.”
Writing in today’s issue of the journal Science, the researchers report that in a healthy cell the newly found protein lives within the central nucleus, where scientists believe it acts as a switch that turns various genes on and off. In the final stages of breast cancer, however, the protein languishes in the cell’s outer regions, unable to perform its functions. That could, in part, be responsible for the haywire growth of cancer cells.
This finding indicates that the gene that produces the protein might play a much more central role in breast cancer than previously thought. Last fall, researchers at the University of Utah won the race to identify that “breast cancer gene,” commonly known as BRCA1. Defects in BRCA1 are believed responsible for half of the inherited cases of breast and ovarian cancer, but only about 2.5% overall. Further research showed that in non-inherited cancers, the gene was undamaged.
“This study provides a clue that BRCA1 might be important in the more common non-hereditary form of breast cancer,” said co-author Kent Osborne, head of the medical oncology division at the University of Texas Health Science Center at San Antonio.
Scientists already knew from information encoded in the BRCA1 gene that the protein existed. What Lee’s group did was build an antibody that could hook onto just this one protein. “You go fishing, you don’t know which fish are going to bite,” Lee said. “Here we know which one we want.”
To detect the protein they attached fluorescent molecules to the antibody, which acted like bicycle reflectors. When they shined light on the cells under a microscope, the BRCA1 proteins lit up like a Christmas tree. “We were the first to say, ‘Ah, here is the guy,’ ” Lee said.
Like all proteins, the BRCA1 protein is assembled in the cytoplasm, the material surrounding the nucleus. In healthy cells, Lee found that the BRCA1 protein resided exclusively in the nucleus, which means the cell normally shepherds the protein from the cytoplasm into the nucleus.
But in all 17 samples taken from late-stage cancer biopsies, the protein remained in the cytoplasm. Both the BRCA1 gene and protein were undamaged, but the transportation system had broken down. “This protein is intact,” Lee said. “It’s just stuck in the wrong place.”
Over the next couple years, Lee will study about 1,000 samples of breast and ovarian cancer cells in search of a correlation between where the protein is and how far the cancer has progressed.
“Maybe we can predict with greater accuracy those patients most likely to have the cancer spread to other parts of the body,” Osborne said, “and then apply more aggressive chemotherapy to these patients.”
In the longer term, Lee said, it may be possible to design a drug to move the errant proteins back into the nucleus or to somehow repair the transport mechanism.
Meanwhile, a separate study adds another point in the debate of when women should start getting mammograms.
Dr. Hiram Cody of Memorial Sloan-Kettering Cancer Center in New York City reports that increased use of mammography--not better examinations by physicians or patients--accounts for the current trend toward earlier detection of tumors. Moreover, he said, the benefit is equally apparent in patients younger and older than age 50.
In the study, which appears in the current issue of the journal Cancer, Cody reviewed the records of 1,096 patients between 1979 and 1993, comparing the size of the tumor to how it was found. “It is only when the diagnosis was by mammogram that the data showed a trend toward earlier diagnosis,” said Cody, a breast cancer surgeon. “The implication is that a mammogram is quite useful for women under age 50.”
“These data are really scarce,” said Robert Smith, senior director of detection and treatment at the American Cancer Society. “No one really collects them.”
