For years, cancer experts have realized that cancerous cells act in certain ways like stem cells, unspecialized cells that whenever exposed to certain signals, can “differentiate. ”

When a stem cell differentiates, it begins down an one-way path that will result in its specialty area and eventually its death. For instance, a stem cell within the breast can become a luminal cell, one of the breast’s “milk factories. ” Such cells have a limited life span. Malignancy cells resemble stem cells not because they can turn straight into other cell types, but because in developmental conditions, they seem to go in the opposite direction: they begin to run through several layers of stop signs and barricades and just continue multiplying.

Assistant Professor Camila dos Santos of Cold Spring Harbor Laboratory (CSHL) is learning stem cells in the breast for clues about what adjustments occur when normal breast cells become cancerous. These days, a team led by dos Santos, in cooperation with Professor Gregory Hannon of Cancer Research UNITED KINGDOM, Cambridge Institute, and Assistant Professor William Pomerantz on the University of Minnesota, identify a protein that they display must be present in order for mammary stem cells to do their normal functions.

When the researchers genetically removed or chemically inhibited the protein, called BPTF, stem cells could no longer maintain their “renewing” condition and began to take on the character of specialized breast cellular material — and then soon died.

“That had been very exciting for us, ” says dos Santos, “because that’s exactly what were want to drive breast cancer cells to undertake. We want to take away their stem cell-like qualities — specifically their ability to multiply indefinitely. We are testing the idea that the drug that inhibits BPTF might have the same effect within cancer cells as in stem cells -it could cause these to differentiate and then die. ”

When learning how normal cells change into cancer cells, dos Santos and other cancer researchers pay close attention to gene expression. Every cellular in the breast, including stem cells, contains the full individual genome. One way of thinking about what differentiates a breast cellular from a heart cell is that each cell type communicates different subsets of genes.

The same can also be true within each organ. In the breast, the system designed to carry milk during and after pregnancy are composed associated with two highly specialized cell types and a niche associated with stem cells that gives rise to both types. All these different cell types expresses different groups of genes on different times over the lifespan of an individual.

The hollow “tube” that forms the milk duct is built from luminal cells; these are surrounded by a slim layer of cells called myoepithelial cells. Receptors on top of the myoepithelial cells are designed to interact with a hormone, oxytocin, released during lactation. This interaction causes the myoepithelial cells — on the outer layer of the ductal framework — to contract, squeezing the luminal cells inside. Those luminal cells are the breast’s milk factories.

BPTF’s epigenetic role in exposing plus hiding genes

BPTF, identified simply by Dos Santos and colleagues as essential for mammary originate cell maintenance, is a protein with a very specialized perform. It is what biologists call a chromatin remodeling element. Chromatin is the packaging that enables six linear feet associated with DNA in each of our cells to be compressed inside the tiny nucleus.

With so much DNA squished directly into such a small space, it stands to reason that expressing the gene in the “middle” of the bundle might require loosening the particular packing material to expose that segment of DNA towards the machinery that copies it into an RNA chemical. This copying is the first step in using the gene’s “blueprint” to manufacture a needed protein. Chemical modifications in order to chromatin — and even more specifically, to the histone proteins that offer “spools” around which the DNA is wound — these are known as epigenetic modifications.

“It has become very clear the opening up or tightening of chromatin, to expose or conceal genes in our chromosomes, plays a role in cancer progression, ” 2 Santos says. “For instance, exposing a gene in a particular moment might help a cancer cell bypass the ‘stop sign’ in a growth pathway. ”

The research published today shows that BPTF is part of the regulatory system that opens chromatin and changes gene expression, specifically in mammary stem cells. This starting of the chromatin turns out to be critical in the ability of the originate cell to remain “immortal” — to give rise to girl stem cells that will also help maintain a tissues such as the breast, and seeding it, at different instances of life, with specialized cells. For example , during puberty, when the breast develops, or during pregnancy, when the breast things up to produce milk.

“We now understand that mammary stem cells are highly dependent on BPTF. The following task it to explore if can we use that will dependency to target stem cell-like programs in breast cancer tissue, ” dos Santos says.