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!
More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn
How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.
We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
19.01.2018 | Materials Sciences
19.01.2018 | Health and Medicine
19.01.2018 | Physics and Astronomy