Investigating the role of AMPK in mammary gland alveologenesis and lactation

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PhD; 2022; Molecular reproduction, development and genetics

AMP-activated kinase (AMPK) is an energy sensor that regulates cell growth and metabolism. Reports from our laboratory and others have shown the context-specific role of AMPK signaling in breast cancer. However, its role in normal mammary gland growth and function is unclear. Here, we showed that AMPK expression and activity within murine mammary epithelia increased from puberty to pregnancy, reaching its highest levels during lactation, and then declined post-lactation. Further, induction of prolactin (PRL) signaling increased AMPK expression and activity in ex vivo organotypic cultures of mammary epithelial cells (MECs), whereas PRL failed to do so in 2D monolayer culture of MECs. To understand the role of AMPK in mammary gland morphogenesis in vivo, we generated mice with conditional knockout of the catalytic AMPK isoforms 1 and 2 (AMPK⍺1,⍺2 homo cDKO) in mammary gland. Whole mount analysis of AMPK⍺1,⍺2 homo cDKO mammary glands demonstrated precocious alveolar development with increased epithelial content due to enhanced proliferation and altered differentiation.