Nav: Home

A surplus with consequences

August 04, 2016

The transcription factor Myc has two faces: On the one hand, the protein is indispensable for cell growth and division. On the other hand, it is prevalent in virtually all cancer cells - however in a much higher concentration. So it is obvious to suspect Myc of playing a key role when cells turn cancerous. However, there have been conflicting theories as to how this process takes place in detail.

Study at the Biocenter

A new study conducted by Würzburg scientists now presents what's going on inside cells in a new light. According to the study, high levels of the Myc proteins are the prerequisite for tumour genesis. The study was conceived at the Department of Biochemistry and Molecular Biology (Chair: Prof. Dr. Martin Eilers) of the University of Würzburg; junior team leader Dr. Elmar Wolf is in charge of the study.

"We studied cells that have both a very low level of Myc and are well understood in terms of molecular biology," says Elmar Wolf. The scientists gradually increased the Myc level in these cells and subsequently investigated the consequences. They then validated their findings in real tumours.

The concentration regulates the function

"According to previous doctrine, the transcription factor Myc activates a number of genes which are responsible for cell growth and division," Wolf explains. As in the intestine for example: The cells of the intestinal mucosa have a very short life-span due to the harsh conditions prevailing there. Therefore, the cells of the intestinal epithelium are continuously renewed about once a week - which is a straightforward process when Myc levels are normal. But when excessive amounts of Myc are produced in a cell, these genes are also much more active, transforming the cell into a tumour cell - so the previous notion. A view not shared by Elmar Wolf: "In reality, the processes are much more complex."

Actually, Myc not only regulates the expression of known genes in tumour cells. Wolf and his team were able to demonstrate that the protein binds to other genes as its level increases and enhances their transcription. "In normal concentrations, Myc binds to certain genes with a high affinity. As the concentration rises, however, it also regulates genes with a low affinity," Wolf explains the principle. Depending on the concentration, the scientists found different gene regulation patterns that each trigger different processes.

Major contribution to tumour growth

"High affinity": This includes genes that control cell growth and division. "Low affinity": These are genes regulated by Myc that control processes which promote other aspects of tumour growth. "For example, the tumour must be supplied with nutrients in order to grow. To do so, it needs blood vessels," Wolf explains. And Myc only binds to the genes responsible for creating new blood vessels once it has reached a high level in the tumour cell.

Migration is another example of such a process Myc triggers by activating low-affinity genes. It enables tumour cells to migrate to other parts of the body and create metastases.

New target for tumour therapy

The observation that Myc has a different impact in healthy persons (regulating the expression of genes with a "high affinity") and in tumours (regulating the expression of genes with a "low affinity") opens up new fascinating possibilities in tumour therapy according to the scientists: "If there was a drug to inhibit the function of Myc, our study suggests that there should be a dose that would curb the tumour-promoting properties of Myc while preserving important functions of Myc for the healthy tissue," says Elmar Wolf.

Unlike standard chemotherapy drugs that target rapidly dividing cells, as are found in the intestinal mucosa, such a therapeutic approach would drastically reduce the side effects of treatment. At present, however, no such drugs are available to inhibit the function of Myc. But international researchers are working feverishly to achieve this goal.
-end-
Different promoter affinities account for specificity in Myc-dependent gene regulation. Francesca Lorenzin, Uwe Benary, Apoorva Baluapuri, Susanne Walz, Lisa Anna Jung, Björn von Eyss, Caroline Kisker, Jana Wolf, Martin Eilers, Elmar Wolf. DOI: 10.7554/eLife.15161.001

University of Würzburg

Related Blood Vessels Articles:

Study: Use of prefabricated blood vessels may revolutionize root canals
Researchers at OHSU in Portland, Oregon, have developed a process by which they can engineer new blood vessels in teeth, creating better long-term outcomes for root canal patients and clinicians.
New findings on formation and malformation of blood vessels
In diseases like cancer, diabetes, rheumatism and stroke, a disorder develops in the blood vessels that exacerbates the condition and obstructs treatment.
Targeting blood vessels to improve cancer immunotherapy
EPFL scientists have improved the efficacy of cancer immunotherapy by blocking two proteins that regulate the growth of tumor blood vessels.
Reprogrammed blood vessels promote cancer spread
Tumor cells use the bloodstream to spread in the body.
Neurons modulate the growth of blood vessels
A team of researchers at Karlsruhe Institute of Technology shake at the foundations of a dogma of cell biology.
Sensor for blood flow discovered in blood vessels
The PIEZO1 cation channel translates mechanical stimulus into a molecular response to control the diameter of blood vessels.
Blood vessels control brain growth
Blood vessels play a vital role in stem cell reproduction, enabling the brain to grow and develop in the womb, reveals new UCL research in mice.
No blood vessels without cloche
After 20 years of searching, scientists discover the mystic gene controlling vessel and blood cell growth in the embryo.
New way of growing blood vessels could boost regenerative medicine
Growing tissues and organs in the lab for transplantation into patients could become easier after scientists discovered an effective way to produce three-dimensional networks of blood vessels, vital for tissue survival yet a current stumbling block in regenerative medicine.
Regenerating blood vessels gets $2.7 million grant
Biomedical engineers in the Cockrell School of Engineering at The University of Texas at Austin have received $2.7 million in funding to advance a treatment that regenerates blood vessels.

Related Blood Vessels Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#529 Do You Really Want to Find Out Who's Your Daddy?
At least some of you by now have probably spit into a tube and mailed it off to find out who your closest relatives are, where you might be from, and what terrible diseases might await you. But what exactly did you find out? And what did you give away? In this live panel at Awesome Con we bring in science writer Tina Saey to talk about all her DNA testing, and bioethicist Debra Mathews, to determine whether Tina should have done it at all. Related links: What FamilyTreeDNA sharing genetic data with police means for you Crime solvers embraced...