Expression of Brca1 and splice variant Brca1 Delta 11 RNA levels in mouse mammary gland during normal development and tumorigenesis

Expression of Brca1 in mouse mammary cancer has yet to be analysed. We use a progressive model of neoplasia based on several mouse epithelial cell lines that represent distinct steps toward the fully tumorigenic state. Using RNase protection analysis because acceptable anti-Brca1 antibodies are not available we investigated the expression of Brca1 and a splice variant, Brca1 Delta 11, in several mammary hyperplasias and tumors that arose from them, and in normal mammary gland through pregnancy and involution. Expression of Brca1 was highest in rapidly proliferating cells. Expression of the full-length Brca1 was detectable in the virgin gland, was slightly elevated in the midpregnant gland, and decreased to levels similar to the age-matched virgin gland in the completely involuted gland. Expression of both forms of Brca1 was detectable in 9/9 paired hyperplasias and tumors, with levels of total Brca1, but not the splice variant Brca1 Delta 11, in tumors higher than those in the hyperplasias. While in disagreement with the observation that Brca1 levels decrease in human breast cancer progression, these patterns support the notion that Brca1 expression is associated with proliferating cells, and suggests that the link with differentiation seen in normal cells can be removed when cells become tumorigenic.