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Tumor suppressor gene in flies may provide insights for human brain tumors
June 23, 2009SINGAPORE and DURHAM, N.C. - In the fruit fly's developing brain, stem cells called neuroblasts normally divide to create one self-renewing neuroblast and one cell that has a different fate. But neuroblast growth can sometimes spin out of control and become a brain tumor.
Researchers at Duke-NUS Graduate Medical School in Singapore have found a tumor-suppressing protein in the fly's brain, with a counterpart in mammals, that can apparently prevent brain tumors from forming.
"Our data explicitly show that the fruitfly protein PP2A (protein phosphatase 2A) suppresses brain tumor formation and controls the balance of self-renewal and differentiation of neural stem cells," said Hongyan Wang, Ph.D, assistant professor of neuroscience and behavioral disorders, and senior author of a paper published online in the journal Development.
"Given that mechanisms for stem cell division in flies and mammals are likely to be similar, our study on fly PP2A may provide useful insights for certain types of human brain tumors and possibly in a wide variety of cancers," Wang said.
By studying flies that had a PP2A mutation, the researchers learned that flies with missing or abnormally expressed PP2A had ten times the amount of stem cell growth in their larval brains. The flies' neural stem cells did not become neurons (nerve cells) in the brain, the types of cells needed for normal function. Instead, they effectively grew into a tumor mass.
Dr. Wang's previous work had identified a protein kinase called Polo as a tumor suppressor. Because phosphatases like PP2A usually have the opposite biochemical function to kinase, the scientists predicted that PP2A would stop the tumor suppressor Polo and allow for unchecked cell growth. "We were very surprised when we found that PP2A also suppressed tumors," Wang said.
Follow-up experiments showed that PP2A is important for regulating Polo kinase function, and showed that these two critical brain tumor suppressors work together to control neural stem cell divisions.
"Our discovery suggests that PP2A and Polo, both of which are crucial brain tumor-suppressors and cell cycle regulators, can function in the same pathway to regulate stem cell self-renewal and tumor development," Wang said. The research team plans to uncover novel proteins in this pathway by learning which protein functions between PP2A and Polo during the neural stem cell division process.
Duke University Medical Center
"Given that mechanisms for stem cell division in flies and mammals are likely to be similar, our study on fly PP2A may provide useful insights for certain types of human brain tumors and possibly in a wide variety of cancers," Wang said.
By studying flies that had a PP2A mutation, the researchers learned that flies with missing or abnormally expressed PP2A had ten times the amount of stem cell growth in their larval brains. The flies' neural stem cells did not become neurons (nerve cells) in the brain, the types of cells needed for normal function. Instead, they effectively grew into a tumor mass.
Dr. Wang's previous work had identified a protein kinase called Polo as a tumor suppressor. Because phosphatases like PP2A usually have the opposite biochemical function to kinase, the scientists predicted that PP2A would stop the tumor suppressor Polo and allow for unchecked cell growth. "We were very surprised when we found that PP2A also suppressed tumors," Wang said.
Follow-up experiments showed that PP2A is important for regulating Polo kinase function, and showed that these two critical brain tumor suppressors work together to control neural stem cell divisions.
"Our discovery suggests that PP2A and Polo, both of which are crucial brain tumor-suppressors and cell cycle regulators, can function in the same pathway to regulate stem cell self-renewal and tumor development," Wang said. The research team plans to uncover novel proteins in this pathway by learning which protein functions between PP2A and Polo during the neural stem cell division process.
Duke University Medical Center
Stem Cell Current Events and Stem Cell News RSSFirst reconstitution of an epidermis from human embryonic stem cells
Stem cell research is making great strides. This is yet again illustrated by a study carried out by the I-STEM* Institute (I-STEM/ Inserm UEVE U861/AFM), published in the Lancet on 21 November 2009. The I-STEM team, directed by Marc Peschanski has just succeeded in recreating a whole epidermis from human embryonic stem cells.
Your Own Stem Cells Can Treat Heart Disease
The largest national stem cell study for heart disease showed the first evidence that transplanting a potent form of adult stem cells into the heart muscle of subjects with severe angina results in less pain and an improved ability to walk. The transplant subjects also experienced fewer deaths than those who didn't receive stem cells.
U of M researchers find 2 units of umbilical cord blood reduce risk of leukemia recurrence
A new study from the Masonic Cancer Center, University of Minnesota shows that patients who have acute leukemia and are transplanted with two units of umbilical cord blood (UCB) have significantly reduced risk of the disease returning.
Researchers find potential treatment for Huntington's disease
Investigators at Burnham Institute for Medical Research (Burnham), the University of British Columbia's Centre for Molecular Medicine and Therapeutics and the University of California, San Diego have found that normal synaptic activity in nerve cells (the electrical activity in the brain that allows nerve cells to communicate with one another) protects the brain from the misfolded proteins associated with Huntington's disease.
Researchers 'notch' a victory toward new kind of cancer drug
Scientists have devised an innovative way to disarm a key protein considered to be "undruggable," meaning that all previous efforts to develop a drug against it have failed.
UCI embryonic stem cell therapy restores walking ability in rats with neck injuries
The first human embryonic stem cell treatment approved by the FDA for human testing has been shown to restore limb function in rats with neck spinal cord injuries - a finding that could expand the clinical trial to include people with cervical damage.
First use of antibody and stem cell transplantation to successfully treat advanced leukemia
For the first time, researchers at Fred Hutchinson Cancer Research Center have reported the use of a radiolabeled antibody to deliver targeted doses of radiation, followed by a stem cell transplant, to successfully treat a group of leukemia and pre-leukemia patients for whom there previously had been no other curative treatment options.
Immune therapy can protect against or treat later lymphoma
Specially developed immune system cells that target the common Epstein-Barr virus can protect immune-suppressed bone marrow transplant recipients against lymph system disease and cancers that arise from the viral infection.
Immunotherapy demonstrates long-term success in treating lymphoma
Targeted immunotherapy has been an attractive new therapeutic area for a number of cancers because it has the potential to destroy tumor cells without damaging surrounding normal tissue. New study results demonstrate high success rates using specialized white blood cells to prevent or treat lymphoma associated with the Epstein-Barr virus (EBV-lymphoma) in patients who have received a hematopoietic stem cell transplant (HSCT).
Of mice and men: Stem cells and ethical uncertainties
The recent creation of live mice from induced pluripotent stem cells (iPSCs) not only represents a remarkable scientific achievement, but also raises important issues, according to bioethicists at The Johns Hopkins University's Berman Institute of Bioethics.
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