the brg1 chromatin remodeler protects against ovarian cysts, uterine tumors, and mammary tumors in a lineage-specific manner缺失的染色质重塑预防卵巢囊肿,子宫肿瘤,乳腺肿瘤lineage-specific的方式.pdfVIP

The BRG1 Chromatin Remodeler Protects Against Ovarian Cysts, Uterine Tumors, and Mammary Tumors in a Lineage-Specific Manner 1 2 3,4,5,6 1 1¤a Daniel W. Serber , Allison Rogala , Maisam Makarem , Gary B. Rosson , Karl Simin , Virginia 2 1¤b 3,4,5,6 1 Godfrey , Terry Van Dyke , Connie J. Eaves , Scott J. Bultman * 1 Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, United States of America, 2 Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America, 3 Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada, 4 Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada, 5 Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada, 6 Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada Abstract The BRG1 catalytic subunit of SWI/SNF-related complexes is required for mammalian development as exemplified by the early embryonic lethality of Brg1 null homozygous mice. BRG1 is also a tumor suppressor and, in mice, 10% of heterozygous (Brg1null/+) females develop mammary tumors. We now demonstrate that BRG1 mRNA and protein are expressed in both the luminal and basal cells of the mammary gland, raising the question of which lineage requires BRG1 to promote mammary homeostasis and prevent oncogenic transformation. To investigate this question, we utilized Wap-Cre to mutate both Brg1 floxed alleles in the luminal cells of the m