Research Summary: Cellular Microenvironment Influences the Ability of Mammary Epithelia to Undergo Cell Cycle


The use of cell culture models is a principal and fundamental technology used in
understanding how mammalian cells work. However, for some cell types such as
mammary epithelia, the lines selected for extended culture are often transformed
or have chromosomal abnormalities, while primary cultures have such a curtailed
lifespan that their use is restricted. For example, mammary luminal epithelial
cells (MECs) are used to study mechanisms of breast cancer, but the
proliferation of primary cell cultures is highly limited. Here we describe the
establishment of a new culture system to allow extended analysis of cultures of
primary mouse MECs. In 2D monolayer culture, primary MECs showed a burst of
proliferation 2–3 days post isolation, after which cell cycle decreased
substantially. Addition of mammary epithelial growth factors, such as Epidermal
Growth Factor, Fibroblast Growth Factor-2, Hepatocyte Growth Factor, and
Receptor Activator for Nuclear Factor κB Ligand, or extracellular matrix
proteins did not maintain their proliferation potential, neither did replating
the cells to increase the mitogenic response. However, culturing MECs directly
after tissue extraction in a 3D microenvironment consisting of basement membrane
proteins, extended the time in culture in which the cells could proliferate. Our
data reveal that the cellular microenvironment has profound effects on the
proliferative properties of the mammary epithelia and is dominant over growth
factors. Moreover, manipulating the cellular environment using this novel method
can maintain the proliferative potential of primary MECs, thus enabling cell
cycle to be studied as an endpoint after gene transfer or gene deletion


Publisher: Public Library of Science

Date Published: 29-March-2011

Author(s): Jeanes A., Maya-Mendoza A., Streuli C.


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