Dysfunction of a gene involved in breast development during puberty predisposes to breast cancer

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A team led by researchers from the Higher Council for Scientific Research (CSIC) has discovered that the dysfunction of a key gene for the proper development of the breasts during puberty predisposes to the formation of tumors.

The work, carried out in mice and published in the latest issue of the journal Nature Communications, can contribute to the detection of therapeutic targets for the treatment of breast cancer.

The tissue of the breast is composed of two compartments, the one formed by the mammary ducts, the epithelial ducts responsible for producing and transporting the milk during lactation, and the stroma or connective tissue that surrounds them.

Researchers have discovered a mechanism by which stromal cells regulate the proper development of the breast epithelium during puberty. This phase is controlled globally by hormones and locally by the repetitive and bidirectional communication between the epithelium and the stroma.

“This communication mechanism between epithelial and stromal cells is based on a series of signaling proteins, called Wnt ligands, which are essential for the development of most tissues, but which are also associated with the development of many types of cells. tumors in humans, “explains CSIC researcher Fernando Martín-Belmonte, who works at the” Severo Ochoa “Molecular Biology Center (CSIC-Autonomous University of Madrid).

Gen Sfrp3

The study reveals that the Sfrp3 gene modulates the communication of the epithelial cells and the stroma through Wnt. These proteins favor the proliferation and migration of these cells, but their activity is also necessary for them to differentiate correctly. “We still do not understand what mechanisms are responsible for this duality in Wnt functions. This is essential, since the deregulation of Wnt is associated with many types of tumors, “adds the CSIC researcher.

In the animal model with Sfrp3 dysfunction, the epithelial cells show an increased proliferation, with characteristics of loss of functional identity or polarity and anomalous differentiation, which “shows that Sfrp3 functions as an extracellular transporter of Wnt proteins, in such a way that it controls its accumulation in the border between the epithelium and the stroma, thus modulating the proliferative and migratory response, as well as the branching of the epithelium during the development of the breast “, highlights Martín-Belmonte.


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