Bcor 103 1st Edition Lecture 25 Outline of Last Lecture I Human Genome Project II Gene Studies Outline of Current Lecture I Cancer II Tumor Suppressors Current Lecture Cancer uncontrolled cell growth found in all vertebrates likely occurs in all multicellular organisms Cancer is not a single disease but a family of diseases Lung cancer is by far the leading cause of cancer death among men 28 followed by prostate 9 and colon rectum 8 cancers Among women lung 26 breast 15 and colon rectum 9 cancers are the leading causes of cancer death The risk of an American woman developing cancer over her lifetime is a little more than one in three Presently the risk of an American man developing cancer over his lifetime is a little less than one in two Development of cancer requires multiple genetic changes o Most tumors are clonal as illustrated by x inactivation patterns of tumors Key cancer problem somatic cell evolution o Cancer cells acquire new traits through gene activation inactivation Tumor suppressor genes function lost in cancer cells o genes that control restrict cell growth Oncogenes gain of function in cancer cells o genes that promote cell growth Aneuploidy an abnormal number of chromosomes are a common occurrence in tumors along with deletions duplications and translocations Cancer development is a multi stage process that requires both genetic change mutation and selection Typically 1 in 1000 tumor cells survive upon entry into the circulatory system Selective pressures include hypoxia nutrient deprivation waste accumulation immune response drug therapy Key point tumors are NOT composed of a homogeneous population of cancer cells These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute Carcinogens induce genetic change Some carcinogens such as aflatoxin need to be modified by cellular enzymes often cytochrome P450 family enzymes in order to damage DNA metabolic activation Graph displays the cancer incidence in workers exposed to beta naphthalene over time Tumor development is both dose and time dependent consistent with the acquisition of multiple genetic changes Hiroshima Nagasaki peak incidence of radiation induced leukemia occurred 5 years after use of nuclear weapons Key concept somatic cell evolution Oncogenic viruses introduce new genetic material into the host cell Tumor induction is not part of the viral replication strategy in nearly all cases it represents a dead end for the virus Infection of permissive cells results in cell lysis death following viral replication therefore there is no tumor development Infection of non permissive cells by definition does not result in viral replication Viral DNA may remain in host cell where it may encode proteins that contribute to tumor development Cell transformation does not offer the virus an advantage Many small DNA viruses infect non dividing host cells These viruses utilize the host cell DNA replication machinery to replicate their own genomes Since the host cell DNA replication machinery is only produced in mitotic cells these viruses encode proteins to stimulate host cell proliferation SV40 HPV and adenovirus induce cell division by inactivating the tumor suppressor protein Rb These viruses also encode proteins to inactivate the tumor suppressor p53 Inactivation of Rb results in the release of the active transcription factor E2F which is required for the activation of genes that encode components of the DNA replication machinery as well as genes that encode proteins that are required for entry into S phase Tumor promoters do not induce DNA damage rather they promote the proliferation of cells some of which may contain damaged DNA mutations Thus tumor promoters expand the population of both normal and mutant cells The enlarged population of mutant cells increases the probability of tumor formation Oncogene activating mutations promote mitosis cell cycle progression Tumor suppressor gene loss of function results in loss of cell growth control inability to control the cell cycle