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Identifying the murine mammary cell target of metformin exposure.


ABSTRACT: The heterogeneity of breast cancer makes current therapies challenging. Metformin, the anti-diabetic drug, has shown promising anti-cancer activities in epidemiological studies and breast cancer models. Yet, how metformin alters the normal adult breast tissue remains elusive. We demonstrate metformin intake at a clinically relevant dose impacts the hormone receptor positive (HR+) luminal cells in the normal murine mammary gland. Metformin decreases total cell number, progenitor capacity and specifically reduces DNA damage in normal HR+ luminal cells, decreases oxygen consumption rate and increases cell cycle length of luminal cells. HR+ luminal cells demonstrate the lowest levels of mitochondrial respiration and capacity to handle oxidative stress compared to the other fractions, suggesting their intrinsic susceptibility to long-term metformin exposure. Uncovering HR+ luminal cells in the normal mammary gland as the major cell target of metformin exposure could identify patients that would most benefit from repurposing this anti-diabetic drug for cancer prevention/therapy purposes.

SUBMITTER: Shehata M 

PROVIDER: S-EPMC6527562 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Identifying the murine mammary cell target of metformin exposure.

Shehata Mona M   Kim Hyeyeon H   Vellanki Ravi R   Waterhouse Paul D PD   Mahendralingam Mathepan M   Casey Alison E AE   Koritzinsky Marianne M   Khokha Rama R  

Communications biology 20190520


The heterogeneity of breast cancer makes current therapies challenging. Metformin, the anti-diabetic drug, has shown promising anti-cancer activities in epidemiological studies and breast cancer models. Yet, how metformin alters the normal adult breast tissue remains elusive. We demonstrate metformin intake at a clinically relevant dose impacts the hormone receptor positive (HR+) luminal cells in the normal murine mammary gland. Metformin decreases total cell number, progenitor capacity and spec  ...[more]

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2021-06-04 | GSE176118 | GEO