A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or reduction in its function. In combination with other genetic mutations, this could allow the cell to grow abnormally. The loss of function for these genes may be even more significant in the development of human cancers, compared to the activation of oncogenes.
Retinoblastoma (Rb) is a rare form of cancer that rapidly develops from the immature cells of a retina, the light-detecting tissue of the eye. It is the most common primary malignant intraocular cancer in children, especially those under 3 years old.
An oncovirus or oncogenic virus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, when the term oncornaviruses was used to denote their RNA virus origin. With the letters RNA removed, it now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with tumor virus or cancer virus. The vast majority of human and animal viruses do not cause cancer, probably because of longstanding co-evolution between the virus and its host. Oncoviruses have been important not only in epidemiology, but also in investigations of cell cycle control mechanisms such as the retinoblastoma protein.
The Knudson hypothesis, also known as the two-hit hypothesis, is the hypothesis that most tumor suppressor genes require both alleles to be inactivated, either through mutations or through epigenetic silencing, to cause a phenotypic change. It was first formulated by Alfred G. Knudson in 1971 and led indirectly to the identification of tumor suppressor genes. Knudson won the 1998 Albert Lasker Clinical Medical Research Award for this work.
Alfred George Knudson, Jr. was an American physician and geneticist specializing in cancer genetics. Among his many contributions to the field was the formulation of the Knudson hypothesis in 1971, which explains the effects of mutation on carcinogenesis.
Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnormal cell division. Cell division is a physiological process that occurs in almost all tissues and under a variety of circumstances. Normally, the balance between proliferation and programmed cell death, in the form of apoptosis, is maintained to ensure the integrity of tissues and organs. According to the prevailing accepted theory of carcinogenesis, the somatic mutation theory, mutations in DNA and epimutations that lead to cancer disrupt these orderly processes by interfering with the programming regulating the processes, upsetting the normal balance between proliferation and cell death. This results in uncontrolled cell division and the evolution of those cells by natural selection in the body. Only certain mutations lead to cancer whereas the majority of mutations do not.
Cell division protein kinase 6 (CDK6) is an enzyme encoded by the CDK6 gene. It is regulated by cyclins, more specifically by Cyclin D proteins and Cyclin-dependent kinase inhibitor proteins. The protein encoded by this gene is a member of the cyclin-dependent kinase, (CDK) family, which includes CDK4. CDK family members are highly similar to the gene products of Saccharomyces cerevisiae cdc28, and Schizosaccharomyces pombe cdc2, and are known to be important regulators of cell cycle progression in the point of regulation named R or restriction point.
Cyclin D1 is a protein that in humans is encoded by the CCND1 gene.
Retinoblastoma-like protein 2 is a protein that in humans is encoded by the RBL2 gene.
Transcription factor E2F4 is a protein that in humans is encoded by the E2F4 gene.
Runt-related transcription factor 3 is a protein that in humans is encoded by the RUNX3 gene.
Transcription factor E2F5 is a protein that in humans is encoded by the E2F5 gene.
Ubiquitin carboxyl-terminal hydrolase 6 (USB6), also termed TRE17 and Tre-2, is a deubiquitinating enzyme that in humans is encoded by the hominid USP6 gene located at band 13.2 on the short arm of chromosome 17. Deubiquitinating enzymes (DUBs) are enzymes that act within cells to remove ubiquitins from various functionally important proteins. Ubiquitin enzymes add ubiquitin to these proteins and thereby regulate their cellular location, alter their activity, and/or promote their degradation. By deubiquitinating these proteins, DUBs counter the effects of the ubiquinating enzymes and contribute to regulating the actions of the targeted proteins. In normal adult tissues, USP6 is highly expressed in testicle tissue, modestly expressed in ovarian tissue, and absent or minimally expressed in other tissues. It is also highly expressed in fetal brain tissue. The specific functions of USP6 are poorly defined primarily because its presence is restricted to primates: there are no available animal models to determine the effects of its deletion, although some studies suggest that UPSP6 contributes to normal brain development. In all events, USP6 has gained wide interest because of its abnormally increased expression by the neoplastic cells in various tumors derived from mesenchymal tissue.
AT rich interactive domain 4A (RBP1-like), also known as ARID4A, is a protein which in humans is encoded by the ARID4A gene.
Ubiquitin specific protease 4 (USP4) is an enzyme that cleaves ubiquitin from a number of protein substrates. Prior to the standardization of nomenclature USP4 was known as UNP, and was one of the first deubiquitinating enzymes to be identified in mammals. In the mouse and human the USP4 protein is encoded by a gene containing 22 exons.
Tyler Jacks is a David H. Koch Professor of Biology at the Massachusetts Institute of Technology (MIT), a long-time HHMI investigator, and Founding Director of the David H. Koch Institute for Integrative Cancer Research, which brings together biologists and engineers to improve detection, diagnosis, and treatment of cancer. Dr. Jacks is a member of the board of directors of Thermo Fisher Scientific and Amgen, two of the major biotechnology corporations in the world. He is the President of Break Through Cancer and a member of the Board of Overseers, the larger of two governing boards of Harvard University.
The retinoblastoma protein is a tumor suppressor protein that is dysfunctional in several major cancers. One function of pRb is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide. When the cell is ready to divide, pRb is phosphorylated, inactivating it, and the cell cycle is allowed to progress. It is also a recruiter of several chromatin remodeling enzymes such as methylases and acetylases.
The triangle of death is an area approximately 25 km northeast of the city of Naples in the Province of Naples, Campania, Italy, that comprises the comuni of Acerra, Nola and Marigliano. This area contains the largest illegal waste dump in Europe due to a waste management crisis in the 1990s and 2000s.
Ed Harlow is an American molecular biologist.
J. William Harbour is an American ophthalmologist, ocular oncologist and cancer researcher. He is Chair of the Department of Ophthalmology at the University of Texas Southwestern Medical Center in Dallas. He previously served as the vice chair and director of ocular oncology at the Bascom Palmer Eye Institute and associate director for basic science at the Sylvester Comprehensive Cancer Center of the University of Miami's Miller School of Medicine.
