BRCA1 is localized in cytoplasmic tube-like invaginations in the nucleus

The cellular localization of the BRCA1 protein is still controversial. Jensen et al. localized a 190-kD BRCA1 product with a granin-like sequence predominantly in secretory vesicles in the cytoplasm and considered it to be a secreted growth inhibitor. Chen et al. identified a 220-kD BRCA1 product in the nucleus of normal breast and ovarian cells, but in the cytoplasm of cancer cells. This latter observation has been challenged by Scully et al., who stated that the protein is exclusively nuclear regardless of cell type, consistent with its RING finger sequence and a C-terminal globular domain analogue to a p53-binding domain. These different localizations--cytoplasmic versus nuclear--may be due to different fixation techniques. However, precise data concerning the cellular localization of BRCA1 are needed to understand its function. We have produced and purified antibodies against exon 11 and the C-terminal region of BRCA1.