Mislocation of BRCA1 Gene Linked to Nonfamilial Breast Cancer

SAN ANTONIO--New research suggests that abnormalities in the BRCA1gene may be involved in the pathogenesis of sporadic breast cancersas well as familial breast and ovarian cancers.

The investigators, from the University of Texas Health ScienceCenter at San Antonio, found that in normal breast epithelialcells and in cells from other types of cancer, the BRCA1 proteinis contained in the cell nucleus.

In contrast, BRCA1 was found in the cell cytoplasm in almost allbreast cancer cell lines tested (all derived from advanced, metastaticcancers), as well as in all 17 samples of malignant pleural effusionsfrom breast cancer patients (Science 270:789-791, 1995).

In primary breast tumors, the BRCA1 protein was less likely tobe mislocated: It was found in the nucleus in eight cases, inthe cytoplasm in six, absent in two, and in both cell locationsin 34 samples studied.

"The subcellular mislocation of the BRCA1 protein suggeststhat abnormalities in BRCA1 are fundamental to the genesis orprogression of most breast cancers," said Dr. Wen-Hwa Lee,lead investigator. In sporadic cases, he said, BRCA1 may be inactivatedindirectly by the mislocation of the protein in the cytoplasm,whereas in hereditary breast cancers, the inactivation stems directlyfrom intragenic mutations.

Because the aberration was more likely to be found in metastaticthan in primary breast cancers, the mislocation of the proteincould indicate more aggressive disease. The researchers plan totest this hypothesis by determining the protein location in upto 1,000 tumor cells stored at the university and correlatingthe results with disease outcome.