Targeted disruption of Brca1 in restricted compartments of the mouse mammary epithelia.
Tumours arising in BRCA1 mutation carriers have a characteristic phenotype, the molecular and cellular basis of which is unknown. To address the hypothesis that this phenotype reflects a role for BRCA1 in either in the basal or the stem cell compartments of the mammary epithelia, we have targeted its disruption to K14 and K6a expressing cells of the mouse. Unlike MMTV and WAP driven conditional knockout models of Brca1, these two models did not result in any observable changes in the mammary gland. Our results suggest that BRCA1-associated tumours arise either in K14 and K6a negative basal cells of the mammary gland, or possibly from transdifferentiation of luminal epithelia.
Smart
Chanel E
CE
School of Molecular and Microbial Sciences, University of Queensland, St Lucia, QLD, Australia.
Clarke
Catherine
C
Brooks
Kelly M
KM
Raghavendra
Ashwini
A
Brewster
Brooke L
BL
French
Juliet D
JD
Hetherington
Rehan
R
Fleming
Jean S
JS
Rothnagel
Joseph A
JA
Wainwright
Brandon
B
Lakhani
Sunil R
SR
Brown
Melissa A
MA
D000818:Animals; D019313:BRCA1 Protein / Q000737:chemistry* / Q000378:metabolism; D002454:Cell Differentiation; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D006801:Humans; D008321:Mammary Glands, Animal / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011401:Promoter Regions, Genetic; D013234:Stem Cells / Q000378:metabolism; D019076:Transgenes
D019313:BRCA1 Protein