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Role of epigenetics and STAT5 in breast cancer resistance protein (BCRP/ABCG2) expression in the lactating mammary gland (1141.3)
Author(s) -
Wu Alex,
Dalvi Pooja,
Yang Mingdong,
Turinsky Andrei,
Wang Kelvin,
Butcher Darci,
Egan Sean,
Weksberg Rosanna,
Brudno Michael,
Harper Patricia,
Ito Shinya
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1141.3
Subject(s) - abcg2 , mammary gland , biology , lactation , stat5 , epigenetics , endocrinology , cancer research , medicine , breast cancer , microbiology and biotechnology , atp binding cassette transporter , signal transduction , cancer , gene , transporter , genetics , pregnancy
The multidrug transporter breast cancer resistance protein (ABCG2) is upregulated in the mammary gland during lactation. We have shown that prolactin induces ABCG2 in human breast cancer cells via the recruitment of Signal Transducer and Activator of Transcription‐5 (STAT5) to the human ABCG2 gene. It is unclear if a similar mechanism regulates ABCG2 in vivo. Here we investigated epigenetic and transcriptional mechanisms that may control Abcg2 expression in the lactating mouse mammary gland. Expression profiling of three different Abcg2 mRNA isoforms (E1a, E1b, and E1c) revealed that the E1b isoform is predominately expressed and induced in the lactating mammary gland. Despite this significant induction during lactation, the E1b promoter region in the virgin gland is already hypomethylated and enriched with the open chromatin histone mark H3K4me2. Next we used a forced‐weaning model to stop lactation and to rapidly turn off Stat5 activity in the mammary gland. Within 48h after forced weaning, there was a significant reduction in Abcg2 mRNA expression with a corresponding reduction in Stat5 occupancy at the mouse Abcg2 gene. Taken together, our results suggest that the Abcg2 gene is already poised for expression in the virgin mammary gland and that the binding of Stat5 plays an important role in the regulation of Abcg2 during lactation. Grant Funding Source : Supported by CIHR.