Genetic mutations in our cells accumulate as we age, and carcinomas are associated with alterations in certain key genes, known as tumor suppressor genes and oncogenes. The overexpression of oncogenes disrupts complex cellular signaling pathways and leads to tumor development. However, most oncogenes also play a variety of essential roles in the normal function of a cell. It is extremely difficult to pinpoint the interplay of genetic and cellular events that goes awry when a cell becomes cancerous.
To better understand the intertwined roles of three genes known to be implicated in skin cancer, Professor Andreas Trumpp and PhD student Thordur Oskarsson studied mice that carried a mutated form of one of them, the oncogene Ras. They then genetically engineered mice whose skin cells also lacked another oncogene, c-myc. The c-myc gene is known to be a master regulator in the cell, responsible for controlling several hundred other genes.
Their first surprise was that the mice without the c-myc gene in their skin cells didn't suffer any adverse effects. Unexpectedly, epidermal cells do not require c-myc for survival, normal differentiation or cellular division. However, even more surprising was that these same mice were completely resistant to developing skin cancer, even though they carried the mutated Ras gene, known to drive tumor development. As expected, mice in the control group carrying a normal copy of the c-myc gene developed cancer.
A piece of the puzzle was clearly missing. The researchers found this in a tumor-suppressing gene known as p21. Mutated Ras drastically increases the level of p21 in the cell, and in this way the tumor-causing effects of Ras are held in check, because p21 inhibits uncontrolled proliferation. However, mutated Ras is a vicious oncogene and has found a way to remove the tumor-suppressing effect of p21. It does this by simultaneously driving increased c-myc activity, which in turn eliminates p21. Thus, epidermis with mutated Ras but no c-myc cannot form tumors as p21 remains highly expressed. Trumpp and his colleagues proved the newly uncovered relationship of this cancer threesome by engineering mice lacking both the c-myc and the p21 genes. As predicted, these mice became sensitive to mutated Ras again and developed extensive skin tumors.
"This work is in vivo proof-of-concept of a key pathway in epithelial tumors," remarks Trumpp. "The gene that is truly critical and protects the cells from oncogenic activity is p21. Inhibiting the c-myc pathway was always thought to be unreasonable because this gene is thought to be implicated in so many cellular functions. However, this might prove to be promising avenue for treating existing carcinomas, because it would only affect tumors and not normal skin cells."
Andreas Trumpp | EurekAlert!
Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie
Study overturns seminal research about the developing nervous system
21.04.2017 | University of California - Los Angeles Health Sciences
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...
Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...
Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.
A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
21.04.2017 | Physics and Astronomy
21.04.2017 | Health and Medicine
21.04.2017 | Physics and Astronomy