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BIOL 445 Cancer Biology Spring 2015 Mark Peifer and Bob Duronio BIOL 445 In Bio 445 we combine the approaches of Bio 202 + Bio 205 with the current scientific literature to study the family of diseases known as cancer You may not believe it but by the end of the semester This will make sense! Hanahan and Weinberg, Cell 100:57-70 (2000) Virtually everything you’ll need is found at: http://www.bio.unc.edu/Courses/2015Spring/Biol445/ It’s a REALLY good idea to look through this carefully THIS WEEK AND Check back frequently for updates or changes We will also us the course Sakai site for online quizzes, Blogs, and as a place for a discussion forum BIOL 445 Textbooks -The Biology of Cancer by Robert Weinberg 2nd Edition What are you responsible for? - Lectures (attendance AND participation) - Papers and assigned textbook reading(on website) -Your project- literature search and presentation Grading - Exams (20% X 2 midterms + 25% final) = 75 - Presentations = 15 - Classroom discussion, online and in-class evaluations = 10 Your Project - Choose a topic - Read the posted review paper - Do a thorough literature research, including primary data on the gene and the disease - Make a poster and present it to your peers - The final exam will cover ALL posters Cancer: a family of diseases caused by our own cells gone wrong Cancer is number 2 and rising relative to heart disease! CDC But as we’ll see, Cancer is not one disease, its many ONS=Other nervous system. Source: American Cancer Society, 2009. Lifetime Probability of Developing Cancer, By Site, Men, US, 2007-2009 Site All sites Prostate Risk 1 in 2 1 in 6 Lung and bronchus 1 in 13 Colon and rectum 1 in 19 Urinary bladder 1 in 26 Non-Hodgkin lymphoma 1 in 43 Melanoma 1 in 40 Kidney 1 in 49 Leukemia 1 in 63 Oral Cavity 1 in 67 Stomach 1 in 92 Source: ACS http://www.cancer.org/Cancer/CancerBasics/lifetime-probability-of-developing-or-dying-from-cancer Lifetime Probability of Developing Cancer, By Site, Women, US, 2007-2009 Site Risk All sites Breast 1 in 3 1 in 8 Lung & bronchus 1 in 16 Colon & rectum 1 in 21 Uterine corpus 1 in 38 Non-Hodgkin lymphoma 1 in 52 Melanoma 1 in 63 Pancreas 1 in 69 Ovary 1 in 72 Kidney 1 in 83 Urinary bladder 1 in 87 Source: ACS http://www.cancer.org/Cancer/CancerBasics/lifetime-probability-of-developing-or-dying-from-cancer We are making progress, however!! March 28.2012 Cancer is NOT an infectious disease Cancer is NOT an infectious disease Instead it illustrates the challenge of understanding how genetics and the environment combine to cause disease To understand what goes WRONG, we need to understand how things normally go right Cells within a tissue are normally highly organized and tightly regulated e.g. intestine e.g. skin Cancer: an aberration of normal development Cancer cells exhibit behaviors found in normal cells during development, differentiation, and homeostasis Cancer: an aberration of normal development Cancer cells exhibit behaviors found in normal cells during development, differentiation, and homeostasis However, cancer cells put together suites Of cell behaviors in problematic ways And do so out of normal regulatory controls All cancers have a genetic basis-they are diseases of our own cells gone wrong Sometimes inherited mutations play a role. e.g., Familial adenomatous polyposis (FAP) =inherited predisposition to colon cancer However, most cases result from the Slow accumulation of Somatic mutations Cancer results from a series of mutations, each further altering the cell Lodish et al. Fig. 24-6 The last two years has seen a revolution in our knowledge of the full array of mutations in many tumor types Properties of Cancer Cells Most normal cells have a limited potential to divide senescent cells Normal stem cells can divide indefinitely, but under tight control Differentiated cells Self-renewing stem cell Properties of Cancer Cells Cancer cells are "immortalized”, just like stem cells, but w/o control Differentiated cells Self-renewing stem cell Cancer cell Most Normal cells differentiate But stem cells do NOT differentiate Like normal stem cells Cancer cells do not differentiate tumor Most normal cells stop proliferating under contact inhibition in vitro Figure 20-29 Molecular Biology of the Cell (© Garland Science 2008) in vivo Cancer cells are not under contact inhibition Figure 20-29 Molecular Biology of the Cell (© Garland Science 2008) However cells of early embryos also lack contact inhibition, but then gain it at the mid-blastula transition Normal “Transformed” Cancer cells have alterations in cell adhesion and the cytoskeleton These changes in cell shape and behavior are shared by many migrating cells, including those that Look outmigrate into wound sites Here I Come! Cell from: www.basic.northwestern.edu/ g-buehler/micropl.jpg Late stage cancer cells are invasive normal tissue invasive tumor Figure 20-17 Molecular Biology of the Cell (© Garland Science 2008) Normal cells can be invasive at the right time and place Seward Hung Normal cells that are starved for O2 Induce Angiogenesis Can’t breath! Send Blood vessels Consequences 1. Nutrients and oxygen are supplied to the tissue Cancer Cells also Induce Angiogenesis Consequences 1. Nutrients and oxygen are supplied to the tumor 2. New blood vessels provide as easy way out Some properties of Cancer Cells involve evading normal behaviors that limit growth and prevent damage Normal cells may undergo apoptosis as part of a developmental program when cells become “dangerous” (e.g. DNA damage) Properties of Cancer Cells Cancer cells escape apoptosis blue cells = breast cancer cells yellow cells = apoptotic cells Dave McCarthy and Annie Cavanagh Cancer: an aberration of normal development Cancer cells exhibit behaviors found in normal cells during development, differentiation, and homeostasis However, cancer cells put together suites Of cell behaviors in problematic ways And do so out of normal regulatory controls Properties of Cancer Cells - Cancer cells are "immortalized” - Cancer cells do not form differentiated tissues - Cancer cells are not under contact inhibition - Cancer cells are invasive - Cancer cells escape apoptosis This Lecture - Properties of cancer cells - Tumor progression - What causes cancer? - Accumulation of mutations Cancer develops through gradual changes in cell morphology and properties Figure 20-9 Molecular Biology of the Cell (© Garland Science 2008) Tumor Progression Tumor = abnormal growth of solid tissue benign- self contained malignantinvasive Metastasis is a difficult and dangerous process both for the tumor cell and the host! Figure 20-17 Molecular Biology of the Cell (© Garland Science 2008) This is what you do NOT want Cellular changes required for metastasis Figure 20-44 Molecular Biology of the Cell (© Garland Science 2008) This Lecture - Properties of cancer cells - Tumor progression - What causes cancer? - Accumulation of mutations What Causes Cancer? Cancer : Accumulation of Mutations - Random mutations (mistakes at the assembly line or induced by environment) - Inherited mutations (pre-disposition) - Viral infections (cervical cancer and a few rare types) The first association between occupation and cancer Percivall Pott found that chimney sweeps show substantially higher rates of skin cancer British chimney sweeps didn’t do anything about it Danish chimney sweeps : a daily bath after work Result: significantly lower rates of skin cancer amongst Danish versus British chimney sweeps, even a century later A happy Danish chimney sweep at work with the family Yamagiwa took it one step further Coal tar condensates induced skin carcinoma in rabbits Chemicals can directly induce cancer Cancer can be studied in the lab Yamagiwa Figure 2.21b The Biology of Cancer (© Garland Science 2007) Carcinogens = agents that contribute to the formation of a tumor Figure 20-20b Molecular Biology of the Cell (© Garland Science 2008) Can YOU see the trend in the data? This Lecture - Properties of cancer cells - Tumor progression - What causes cancer? - Accumulation of mutations Cancer often starts with a single mutation However One mutation is not enough !! Heard of natural selection? The fact that cancer is a multi-step process is reflected in correlation between age and incidence of cancers Figure 20-7 Molecular Biology of the Cell (© Garland Science 2008) Cancer cells also accumulate chromosomal abnormalities, especially late in the process Figure 20-13 Molecular Biology of the Cell (© Garland Science 2008)