Molecular regulation of angiogenesis and tumorigenesis by signal transduction pathways: evidence of predictable and reproducible patterns of synergy in diverse neoplasms.
A large number of oncogenes, tumor suppressor genes, and signal transduction pathways have been described. Currently, a framework that allows prediction of tumor behavior based upon oncogenes, tumor suppressors, and signal transduction pathways is lacking. In 1869, Mendeleev published a periodic table of elements which allowed prediction of properties of elements based upon atomic weights that allowed prediction of chemical and physical properties of elements yet to be discovered. In this paper, I will discuss recurrent patterns of synergy found in the literature and our laboratory between tumor suppressor genes, oncogenes, and signaling pathways that allows one to predict the signaling pathway in a given tumor based upon the inactivation of a tumor suppressor gene. These patterns can be found in multiple different human neoplasms. Conversely, one can predict the inactivation of a tumor suppressor based upon the activation status of a signaling pathway. This knowledge can be used by a clinician or pathologist with access to immunohistochemistry to make predictions based upon simple technologies and determine the signaling pathways involved in a patient's tumor. These strategies may be useful in the design of prevention and treatment strategies for cancer.
Arbiser
Jack L
JL
Department of Dermatology, Emory University School of Medicine, WMB 5309, 1639 Pierce Drive, Atlanta, GA 30322, USA. jarbise@emory.edu
D017209:Apoptosis / Q000235:genetics; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D019942:Genes, p16; D016158:Genes, p53; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011519:Proto-Oncogenes; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases; D000097782:NF-kappaB-Inducing Kinase
D004268:DNA-Binding Proteins; D020928:Mitogen-Activated Protein Kinases; D017346:Protein Serine-Threonine Kinases; D018808:Transcription Factor AP-1; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases; D000097782:NF-kappaB-Inducing Kinase