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New insight into the genetics of brain tumor formation
March 18, 2008In a G&D paper published online ahead of its April 1 print publication date, Dr. William Kaelin (Dana Farber Cancer Institute) and colleagues identify a potential new neuronal tumor suppressor.
"It has been suspected for decades that the short arm of chromosome 1 harbored one or more tumor suppressor genes because this region is deleted in a variety of tumors, including many neural crest-derived tumors. Our work suggests that KIFB{beta} is one such gene," explains Dr. Kaelin.
Neural crest-derived tumors include neuroblastomas and medulloblastomas, which are the most common malignant pediatric solid tumors, as well as paragangliomas (relatively rare tumors of the sympathetic nervous system) and melanomas, the deadliest form of skin cancer.
Under normal developmental conditions, neural crest cells respond to diminishing growth factor signaling by inducing apoptosis, via a pathway involving the enzyme EglN3. However, the acquisition of mutations that enable cells to avoid apoptosis under low growth factor conditions provide a growth advantage and an effective route to tumorigenesis.
In this issue, Dr. Kaelin and colleagues identify that the protein KIF1B{beta} mediates EglN3-induced neuronal apoptosis, and thus provides a protective effect against the development of neural crest-derived tumors.
Importantly, KIF1B{beta} is positioned on the region of chromosome 1p that is deleted in a number of neural crest-derived tumors. The Kaelin group demonstrated that the supplementation of 1p-deleted neuroblastoma cancer cells with KIF1B{beta} protein is sufficient to restore apoptosis and identified inactivating point mutations in neural crest-derived tumors. They also showed that partial reduction of KIF1B{beta} - but not complete loss - confers protection against apoptosis, perhaps explaining why most 1p deleted tumors still retain the other KIF1B{beta} allele in its normal form.
While further research is needed to delineate the mechanism by which KIF1B{beta} induces apoptosis, this work opens up several avenues for investigation. For example, EglN3 is an oxygen-dependent enzyme that responds to a variety of signals and can be modulated with drug-like molecules. Dr. Kaelin points out that "an intriguing possibility is that an increase in EglN3 activity is responsible for the spontaneous regressions frequently observed in neonates who present with Neuroblastoma (so-called Stage 4S Neuroblastoma). Perhaps, in time, we can mimic this with EglN3 agonists."
Cold Spring Harbor Laboratory
Under normal developmental conditions, neural crest cells respond to diminishing growth factor signaling by inducing apoptosis, via a pathway involving the enzyme EglN3. However, the acquisition of mutations that enable cells to avoid apoptosis under low growth factor conditions provide a growth advantage and an effective route to tumorigenesis.
In this issue, Dr. Kaelin and colleagues identify that the protein KIF1B{beta} mediates EglN3-induced neuronal apoptosis, and thus provides a protective effect against the development of neural crest-derived tumors.
Importantly, KIF1B{beta} is positioned on the region of chromosome 1p that is deleted in a number of neural crest-derived tumors. The Kaelin group demonstrated that the supplementation of 1p-deleted neuroblastoma cancer cells with KIF1B{beta} protein is sufficient to restore apoptosis and identified inactivating point mutations in neural crest-derived tumors. They also showed that partial reduction of KIF1B{beta} - but not complete loss - confers protection against apoptosis, perhaps explaining why most 1p deleted tumors still retain the other KIF1B{beta} allele in its normal form.
While further research is needed to delineate the mechanism by which KIF1B{beta} induces apoptosis, this work opens up several avenues for investigation. For example, EglN3 is an oxygen-dependent enzyme that responds to a variety of signals and can be modulated with drug-like molecules. Dr. Kaelin points out that "an intriguing possibility is that an increase in EglN3 activity is responsible for the spontaneous regressions frequently observed in neonates who present with Neuroblastoma (so-called Stage 4S Neuroblastoma). Perhaps, in time, we can mimic this with EglN3 agonists."
Cold Spring Harbor Laboratory
Tumor Suppressor Current Events and Tumor Suppressor News RSSDiscovery in worms by Queen's researchers points to more targeted cancer treatment
Researchers at Queen's University have found a link between two genes involved in cancer formation in humans, by examining the genes in worms. The groundbreaking discovery provides a foundation for how tumor-forming genes interact, and may offer a drug target for cancer treatment.
Loss of tumor supressor gene essential to transforming benign nerve tumors into cancers
Researchers at UCLA's Jonsson Comprehensive Cancer Center showed for the first time that the loss or decreased expression of the tumor suppressor gene PTEN plays a central role in the malignant transformation of benign nerve tumors called neurofibromas into a malignant and extremely deadly form of sarcoma.
KEAP1 Keeps major cancer-promoting protein at bay
A tumor-suppressing protein snatches up an important cancer-promoting enzyme and tags it with molecules that condemn it to destruction, a research team led by scientists at The University of Texas M. D. Anderson Cancer Center reports this week in the journal Molecular Cell.
Genes signal late-stage laryngeal cancer, poorer outcome
Researchers at Henry Ford Hospital have identified tumor-suppressing genes that may provide a more accurate diagnosis of disease stage and survival for laryngeal cancer patients than current standards.
New study resolves the mysterious origin of Merkel cells
A new study resolves a 130-year-old mystery over the developmental origin of specialized skin cells involved in touch sensation.
Natural compounds, chemotherapeutic drugs may become partners in cancer therapy
Research in the Linus Pauling Institute at Oregon State University suggests that some natural food compounds, which previously have been studied for their ability to prevent cancer, may be able to play a more significant role in treating it - working side-by-side with the conventional drugs that are now used in chemotherapy.
Tumor suppressor pulls double shift as reprogramming watchdog
A collaborative study by researchers at the Salk Institute for Biological Studies uncovered that the tumor suppressor p53, which made its name as "guardian of the genome", not only stops cells that could become cancerous in their tracks but also controls somatic cell reprogramming.
Researchers uncover potential mechanisms to protect against genetic alterations, diseases
Peering into the DNA of tiny yeast, researchers at the Moores Cancer Center at the University of California, San Diego and the San Diego Branch of the Ludwig Institute for Cancer Research have pinpointed a large number of genes that can prevent a type of genetic rearrangement that may lead to cancer and other diseases.
Tumor mutations can predict chemo success
New work by MIT cancer biologists shows that the interplay between two key genes that are often defective in tumors determines how cancer cells respond to chemotherapy.
Unraveling how cells respond to low oxygen
Gary Chiang, Ph.D., and colleagues at Burnham Institute for Medical Research (Burnham) have elucidated how the stability of the REDD1 protein is regulated.
More Tumor Suppressor Current Events and Tumor Suppressor News Articles
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The p53 Tumor Suppressor Pathway and Cancer (Protein Reviews, Vol. 2) by Gerard P. Zambetti (Editor) The p53 tumor suppressor gene is mutated in approximately half of all human malignancies, including colon, lung, and breast cancers. It is well recognized that these mutations directly inactivate p53 tumor suppressor function. Furthermore, the p53 protein operates within a pathway and this pathway, including the mutations in p53, is likely inactivated by nearly every human tumor. In support of this hypothesis, 100% of mice that have been engineered such that they do not express p53 protein (knockout animals), develop highly malignant tumors by only 3-6 months of age. The importance of p53 in preventing human cancer is also evident by families in which a mutated p53 gene is inherited from a parent. Individuals who carry an inherited germline p53 mutation are associated with Li-Fraumeni... |
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Benign Prostatic Hyperplasia AHCPR Clinical Practice Guideline/Tumor Suppressor Genes in Human Cancer (NCME Video 658) Also With: Network For Continuing Medical Education (Primary Contributor), John Wasson (Primary Contributor), Daniel A Haber (Primary Contributor) In February, 1994, the Agency for Health Care Policy and Research (AHCPR) released a clinical practice guideline dealing with the diagnosis and treatment of benign prostatic hyperplasia. This telecourse presents highlights of that guideline. In the 1980's, the study of positive oncogenes was a major focus in the quest to understand the molecular origins of cancer. Today, tumor suppressor genes are sharing the spotlight and may exemplify an untapped resource for anticancer therapy. Dr. Haber demonstrates how recessive oncogenes, which normally control cell growth, allows cells to progress to malignancy when lost or inactivated. |
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Tumor Suppressor Genes by Katherine R. Polinsky (Editor) A tumour suppressor gene is a gene that reduces the probability that a cell in a multicellular organism will turn into a tumor cell. A mutation or deletion of such a gene will increase the probability of the formation of a tumor. Unlike oncogenes, tumor suppressor genes generally follow the 'two-hit hypothesis', which implies that both alleles that code for a particular gene must be affected before an effect is manifested. This is due to the fact that if only one allele for the gene is damaged, the second can still produce the correct protein. However, there are cases where mutations in only one allele will cause an effect. A notable example is the gene that codes for p53. Tumor suppressor genes, or more precisely, the proteins for which they code, either have a dampening or repressive... |
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Tumor Suppressors: Involvement in Human Diseases, Viral Protein Interactions and Growth Regulation (Molecular Biology Intelligence Unit) by John W. Ludlow (Author), Gary R. Skuse (Author) | |
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Tumor Suppressor Genes: An entry from Macmillan Reference USA's Macmillan Reference USA Science Library: Genetics by Giles Watts (Author) This digital document is an article from Macmillan Reference USA Science Library: Genetics, brought to you by Gale®, a part of Cengage Learning, a world leader in e-research and educational publishing for libraries, schools and businesses. The length of the article is 1047 words. The article is delivered in HTML format and is available in your Amazon.com Digital Locker immediately after purchase. You can view it with any web browser. A comprehensive collection of articles on all aspects of genetics, from Mendel to the decoding of the human genome. Explains the workings of genes and chromosomes, genetic diseases, and biotechnology. Covers the ethical, legal, and social issues connected to genetic science and includes coverage of careers in the field. | |
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Tumor suppressor gene inactivation during cadmium-induced malignant transformation of human prostate cells correlates with overexpression of de novo DNA ... from: Environmental Health Perspectives by Lamia Benbrahim-Tallaa (Author), Robert A. Waterland (Author), Anna L. Dill (Author), Mukta M. Webber (Author), Michael P. Waalkes (Author) This digital document is an article from Environmental Health Perspectives, published by Thomson Gale on October 1, 2007. The length of the article is 4339 words. The page length shown above is based on a typical 300-word page. The article is delivered in HTML format and is available in your Amazon.com Digital Locker immediately after purchase. You can view it with any web browser. Citation Details Title: Tumor suppressor gene inactivation during cadmium-induced malignant transformation of human prostate cells correlates with overexpression of de novo DNA methyltransferase.(Research)(deoxyribonucleic acid)(Clinical report) Author: Lamia Benbrahim-Tallaa Publication: Environmental Health Perspectives (Magazine/Journal) Date: October 1, 2007 Publisher: Thomson... | |
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Oncogenes and Tumor Suppressor Genes in Human Malignancies (Cancer Treatment and Research) by C.C. Benz (Editor), E.T. Liu (Editor) This volume begins by reviewing selected malignancies in which the search for clinically relevant oncogenes has led to more focused studies on gain-of-function and loss-of-function genetic abnormalities, as well as autocrine and paracrine growth factor loops known to regulate tumor physiology and malignant cell behavior. Many of these genetic and functional abnormalities are shared by several different tumor types and are not uniformly present in all tumors of the same type. This observation brings up molecular questions about the tissue-specific determinants that underlie individual cancers and also gives added impetus to the suggestion that molecular abnormalities (referred to as tumor markers) be included among the histopathologic features used for clinical diagnosis and... | |
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Tumor Suppressor Genes (Immunology Series) by George Klein (Editor) | |
![Molecular processes of chromosome 9p21 deletions causing inactivation of the p16 tumor suppressor gene in human cancer: Deduction from structural analysis ... for deletions [An article from: DNA Repair]](http://ecx.images-amazon.com/images/I/51FZ3K9Y7XL._SL160_.jpg) |
Molecular processes of chromosome 9p21 deletions causing inactivation of the p16 tumor suppressor gene in human cancer: Deduction from structural analysis ... for deletions [An article from: DNA Repair] by T. Kohno (Author), J. Yokota (Author) This digital document is a journal article from DNA Repair, published by Elsevier in 2006. The article is delivered in HTML format and is available in your Amazon.com Media Library immediately after purchase. You can view it with any web browser. Description: Chromosome interstitial deletion (i.e., deletion of a chromosome segment in a chromosome arm) is a critical genetic event for the inactivation of tumor suppressor genes and activation of oncogenes leading to the carcinogenic conversion of human cells. The deletion at chromosome 9p21 removing the p16 tumor suppressor gene is a genetic alteration frequently observed in a variety of human cancers. Thus, structural analyses of breakpoints for p16 deletions in several kinds of human cancers have been performed to elucidate the... |
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Tumor Suppressor Genes and Cell Proliferation Control in the Carcinogenesis of the Oral Mucosa by Sabine Christiane Girod (Author) This text is aimed at those involved with cancer research, particularly those interested in epithelial cancers of the aerodigestive tract accounting for one third of all cancer deaths each year. The recent discovery of two groups of genes, oncogenes and tumour suppresor genes has thrown doubt on the possibility of a genetic predisposition in all cases. The current knowledge and recent results concerning the role of tumour suppressor genes in oral carcinogenesis are described, as is the importance of understanding the basic principles and the application of molecular biology techniques. |
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