The gene, called GATA-3, is in a family of genes that guides development of stem cells into mature cells. University of California, San Francisco researchers have now found that GATA-3 is also required for mature mammary cells to remain mature in the adult. In research focusing on mice mammary glands, they found that without GATA-3, mature cells revert to a less specialized, “undifferentiated” state characteristic of aggressive cancer.
The new finding suggests that this gene may play a key role in the development of breast cancer, the scientists report in the December 1 issue of the journal CELL.
Cancer researchers know that breast cancers with high GATA-3 expression have a good prognosis. The cancers tend to be well-differentiated – retaining estrogen receptors and other characteristics of normal mature breast cells. Cancers with low GATA-3 expression tend to be poorly differentiated, with a poor prognosis. The new research may explain why this is so.
“Perhaps the loss of GATA-3 and subsequent failure to maintain this mature state is what leads to loss of differentiation during cancer progression,” said Hosein Kouros-Mehr, PhD, a medical student at UCSF and lead author of the new study. “This gene is part of the instruction manual that controls how a stem cell can mature into a normal mammary cell and remain that way for its lifetime. The finding suggests that the differentiation, or maturity, of cells is a process that must be actively maintained throughout the lifetime of an organism.”
How GATA-3 controls cell fate, and its possible role in breast cancer is now the focus of the team's research.
The UCSF study is part of the work of the Bay Area Breast Cancer and the Environment Research Center, one of four centers funded by the National Cancer Institute and the National Institute of Environmental Health Sciences.
The UCSF scientists found that when the GATA-3 gene activity was knocked out in adult mice, the mammary ductal cells - the principal cell type in breast cancer - regressed to a less differentiated state, which is one of the hallmarks of invasive, metastatic cancer. The cells began to proliferate uncontrollably and then died within the ducts of the mammary gland, they reported.
Previously, little was known about the differentiation of the ductal cells, also known as luminal cells, which form the lining of the breast ducts that carry milk during lactation. The researchers carried out a screen of all genes active in the mammary ducts during puberty and found that GATA-3 was the most abundant transcription factor – a gene that directs the activation of other genes. They further found the GATA-3 protein in all luminal cells of mature mammary ducts, both in mice at puberty and in adult virgin mice.
“We are very excited because we now know that it is not enough for cells to become breast cells but they need an active program to remain in their specialized state and perhaps be kept from wandering off,” said Zena Werb, PhD, professor and vice chair of anatomy and senior author of the paper. “Maybe we should view cancer as telling us what cells become if they lose their ‘homesteading’ genes and then start wandering.”
The scientists hope that further investigation of the precise role of GATA-3 in breast cancer can identify new ways of understanding, diagnosing and treating the disease.
Bare bones: Making bones transparent
27.04.2017 | California Institute of Technology
Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
27.04.2017 | Life Sciences
27.04.2017 | Physics and Astronomy
27.04.2017 | Earth Sciences