A gene that appears to help regulate normal embryonic development is found at high levels in virtually all forms of breast cancer, according to a new study led by Laszlo Radvanyi, Ph.D., associate professor of breast and melanoma medical oncology at The University of Texas M. D. Anderson Cancer Center.
The finding, published in the Aug. 2, 2005, issue of the Proceedings of the National Academy of Sciences and available on-line July 25, shows that the gene, normally made in small amounts in normal breast tissue, somehow becomes over-expressed in breast cancer cells. Researchers hope to use the cancer-specific protein to train the immune system to specifically attack breast cancer cells.
"There is a tremendous need for new molecular targets to treat breast cancer," Radvanyi says. "There are very few bona fide targets that are exquisitely specific for breast cancer. We believe this is one of them."
Radvanyi and his collaborators at Sanofi Pasteur, Toronto, Canada, zeroed in on the gene, called TRPS-1, after an exhaustive search for targets that are found at higher levels in breast cancer than in normal tissue. The researchers compared the gene levels of more than 50,000 known genes in 54 breast cancer specimens and 289 normal samples representing 75 tissues or organs. The breast cancer specimens included 10 examples of early breast cancer or ductal carcinoma in situ (DCIS), 38 locally invasive breast cancers and six representing metastatic disease. They narrowed down their search by eliminating genes commonly found in normal tissue and those predicted to encode proteins that are excreted from the cell.
"We were interested in identifying proteins that could be potential tumor antigens activating cytotoxic T-cells or tumor killer cells," Radvanyi says. "We wanted proteins that would make good targets for a cancer vaccine."
Finally, they zeroed in on TRPS-1, a gene they found at high levels in all forms of breast cancer, from DCIS to invasive disease, but in none of the normal tissues tested, except for low levels found in normal breast tissue.
The TRPS-1 gene turned out to be associated with a rare, inherited genetic disease in which loss of the gene function results in muscle and bone deformities. The gene is located on human chromosome 8 in a region previously known to be associated with breast cancer and other oncogenes. The scientists don't yet know what the TRPS-1 protein is doing during the development of breast cancer, but they have started gathering clues to its role. Scientists at other institutions have shown TRPS-1 is a DNA-binding protein that regulates how other proteins get produced. It also appears to be involved in recognition of steroids such as estrogen. Radvanyi speculates that the protein may help regulate cell growth and perhaps estrogen recognition.
"Based on our findings, we believe that TRPS-1 is involved in the earliest stages of breast cancer," he says.