SAN ANTONIO--New research suggests that abnormalities in the BRCA1
gene may be involved in the pathogenesis of sporadic breast cancers
as well as familial breast and ovarian cancers.
The investigators, from the University of Texas Health Science
Center at San Antonio, found that in normal breast epithelial
cells and in cells from other types of cancer, the BRCA1 protein
is contained in the cell nucleus.
In contrast, BRCA1 was found in the cell cytoplasm in almost all
breast cancer cell lines tested (all derived from advanced, metastatic
cancers), as well as in all 17 samples of malignant pleural effusions
from breast cancer patients (Science 270:789-791, 1995).
In primary breast tumors, the BRCA1 protein was less likely to
be mislocated: It was found in the nucleus in eight cases, in
the cytoplasm in six, absent in two, and in both cell locations
in 34 samples studied.
"The subcellular mislocation of the BRCA1 protein suggests
that abnormalities in BRCA1 are fundamental to the genesis or
progression of most breast cancers," said Dr. Wen-Hwa Lee,
lead investigator. In sporadic cases, he said, BRCA1 may be inactivated
indirectly by the mislocation of the protein in the cytoplasm,
whereas in hereditary breast cancers, the inactivation stems directly
from intragenic mutations.
Because the aberration was more likely to be found in metastatic
than in primary breast cancers, the mislocation of the protein
could indicate more aggressive disease. The researchers plan to
test this hypothesis by determining the protein location in up
to 1,000 tumor cells stored at the university and correlating
the results with disease outcome.