The BRG1 chromatin remodeler protects against ovarian cysts, uterine tumors, and mammary tumors in a lineage-specific manner.

PloS One
Daniel W SerberS J Bultman

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 (Brg1(null/+)) 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 mammary epithelium of pregnant mice where WAP is exclusively expressed within the mammary gland. Interestingly, we found that Brg1(Wap-Cre) conditional homozygotes lactated normally and did not develop mammary tumors even when they were maintained on a Brm-deficient background. However, Brg1(Wap-Cre) mutants did develop ovarian cysts and uterine tumors. Analysis of these latter tissues showed that both, like the mammary gland, contain cells that normally express Brg1 and Wap. Thus, tumor formation in Brg1 mutant mice appears to be confined to particular cell types that require BRG1 and also express Wap....Continue Reading

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Citations

May 25, 2013·Reproduction : the Official Journal of the Society for the Study of Fertility·Marina ZaitsevaPeter A W Rogers
Oct 19, 2012·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Stephanie L Smith-Roe, Scott J Bultman
Aug 30, 2014·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Jaclyn A BiegelBernard E Weissman
Mar 27, 2015·Journal of Cellular Physiology·Qiong WuAnthony N Imbalzano
Jan 25, 2020·Annual Review of Pathology·Yemin WangDavid G Huntsman
Aug 4, 2016·Oncotarget·Stefanie B Marquez-VilendrerDavid Reisman
Jan 21, 2017·Oncoscience·Stefanie B Marquez-VilendrerDavid N Reisman
Dec 30, 2014·Oncotarget·Stephanie L Smith-RoeScott J Bultman
Apr 20, 2017·Frontiers in Oncology·Jeffrey A NickersonAnthony N Imbalzano
Apr 16, 2019·Expert Review of Anticancer Therapy·Krystal A OrlandoBernard E Weissman
Apr 24, 2018·The American Journal of Pathology·Yasumichi KuwaharaBernard E Weissman

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Methods Mentioned

BETA
FACS
PCR
ELISA
flow cytometry
fluorescence-activated cell sorter

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