Researchers link new molecular culprit to breast cancer progression
(Phys.org)—Johns Hopkins researchers have uncovered a protein "partner" commonly used by breast cancer cells to unlock genes needed for spreading the disease around the body. A report on the discovery, published November 5 on the website of the Proceedings of the National Academy of Sciences, details how some tumors get the tools they need to metastasize.
"We've identified a protein that wasn't known before to be involved in breast cancer progression," says Gregg Semenza, M.D., Ph.D., the C. Michael Armstrong Professor of Medicine at the Johns Hopkins University School of Medicine and director of the Vascular Program at Hopkins' Institute for Cell Engineering. "The protein JMJD2C is the key that opens up a whole suite of genes needed for tumors to grow and metastasize, so it represents a potential target for cancer drug development."
Semenza and his colleagues made their finding when they traced the activity of HIF-1, a protein known to switch on hundreds of genes involved in development, red blood cell production, and metabolism in normal cells. Previous studies had shown that HIF-1 could also be hijacked to switch on genes needed to make breast tumors more malignant.
Would-be tumor cells face a host of challenges as they make the transition from working with their host to working against it, such as the need to evade the immune system and to produce more cancer cells, explains Weibo Luo, Ph.D., an instructor in the Institute for Cell Engineering and Department of Biological Chemistry who led the project. All of these efforts require switching on the right genes for the job.
To learn more about how HIF-1 works, the researchers tested a range of human proteins to see whether they would interact with HIF-1. They then sifted through the 200 resulting hits, looking for proteins involved in chemical changes to sections of DNA that determine whether or not the genes they contain are available for use. "In order for HIF-1 to switch genes on, they have to be available, but many of the genes HIF-1 activates are normally locked down in mature cells," explains Luo. "So we thought HIF-1 must have a partner that can do the unlocking."
That partner turned out to be JMJD2C, Luo says. Delving deeper, the researchers found that HIF-1 switches on the JMJD2C gene, stimulating production of the protein. HIF-1's presence also enables JMJD2C to bind to DNA at other HIF-1 target genes, then loosen those DNA sections, enabling more HIF-1 to bind to the same sites and activate the target genes.
To test the implications of their discovery, the research team injected mice with breast cancer cells in which the JMJD2C protein was not produced. Tumors with depleted JMJD2C were much less likely to grow and metastasize to the lungs, confirming the protein's role in breast cancer progression, says Luo.
"Active HIF proteins have been found in many types of tumors, so the implications of this finding go beyond breast cancer," says Luo. "JMJD2C is both an important piece of the puzzle of how tumors metastasize, and a potential target for anti-cancer therapy."
Other authors of the research report are Ryan Chang, Jun Zhong, Ph.D., and Akhilesh Pandey, M.D., Ph.D., all of the Johns Hopkins University School of Medicine.
More information: www.pnas.org/conte… 109.abstract
Journal reference: Proceedings of the National Academy of Sciences
Provided by Johns Hopkins University
- Understanding cancer energetics Jun 04, 2011 | not rated yet | 0
- How breast cancer spreads: Researchers find key to lymph node metastasis in mice Sep 10, 2012 | not rated yet | 0
- Researchers discover how breast cancer spreads to lung Nov 16, 2011 | not rated yet | 0
- Researchers link cell division and oxygen levels Jun 11, 2011 | not rated yet | 0
- How chemotherapy drugs block blood vessel growth, slow cancer spread Jan 22, 2009 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013 Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
Researchers from London's Kingston University have begun a two-year study which could help prolong the lives of people with colorectal tumours.
Cancer 1 hour ago | 5 / 5 (1) | 0
Transformative research from Western University has identified new hormones in the body which may suppress breast cancer and stimulate the regression of breast tumors.
Cancer 2 hours ago | 5 / 5 (1) | 0
(Medical Xpress)—Curtin University researchers have found evidence that targeting specific cells in the body can reverse the effects of cancer on the immune system.
Cancer 2 hours ago | 5 / 5 (2) | 0
A leading expert in childhood cancer at The University of Nottingham is spearheading a Europe-wide lobby of the European Parliament to try to make it easier for doctors to develop and test new treatments on children and young ...
Cancer 3 hours ago | not rated yet | 0
(AP)—Researchers examining the incidence of brain cancer at jet engine manufacturer Pratt & Whitney in Connecticut say they have found no statistically significant elevations in the rate of cancer among workers.
Cancer 4 hours ago | not rated yet | 0
Saudi Arabia said Friday it would send samples taken from animals possibly infected with a deadly SARS-like virus to the United States for testing in a bid to find the source of disease.
52 minutes ago | not rated yet | 0
(Medical Xpress)—A new study by researchers in the US has shown that an ancient virus can be modified to help in the fight against the simian immunodeficiency virus SIV, which is the equivalent in monkeys ...
1 hour ago | 5 / 5 (1) | 0 |
New research presented today shows that formation of new neurons in the hippocampus - a brain region known for its importance in learning and remembering - could cause forgetting of old memories by causing a reorganization ...
1 hour ago | not rated yet | 0
Ernie Pyle – an iconic war correspondent in World War II – reportedly said "There are no atheists in foxholes." A new joint study between two brothers at Cornell and Virginia Wesleyan found that only ...
1 hour ago | 3 / 5 (1) | 0
How can healthy people who hear voices help schizophrenics? Finding the answer for this is at the centre of research conducted at the University of Bergen.
1 hour ago | 3 / 5 (1) | 1
The individualisation of drug treatments to support patients to self-manage their conditions is a concept that sits at the heart of policy, but a recent study in BMJ Open shows that there is no concrete defini ...
1 hour ago | not rated yet | 0