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CANCER MODULE Thank you, Revati Masilamani! CANCER MODULE OVERVIEW • Entire workbook pdf is posted on my web page You are welcome to download units covered in the module or the entire workbook but it is not required. • You will need to take notes from your classroom table discussions • Each table will work together to learn/discuss the material assigned for each quiz. • The table quiz will be given at the beginning of the period on the indicated day. Please Note: If you are absent, you are required to make up the missed assessment individually • On Blockday, 3/1 or 3/2, you will complete an individual summative assessment covering the entire module plus information over the Genomics lectures. CANCER MODULE SCOPE & SEQUENCE DAY UNITS TOPICS FORMATIVE ASSIGNMENTS Block - Fri 1.1 - 1.3 Intro Table Worksheet Tue, 2/21 2.2 – 2.5 Cell Review XXX Block, 2/22 or 2/23 Block, 2/22 – Mon, 2/27 Table Quiz 3.1 – 3.4, 4.2, 5.5 Cancer Metastasis & Treatment Tue Tue XXX Table Quiz All All Loop Review Table Quiz Individual Summative Assessment → Block, 3/1 or 3/2 **Questions from Cancer Module + Genomics Information** WHAT IS CANCER? WHAT IS CANCER, cont WHAT IS CANCER, cont • Tumor versus Cancer o Benign tumor o Malignant tumor Metastasis CANCER MODULE Units 1.3, 2.2, 2.3, 2.4, 2.5 REGULATION OF THE CELL CYCLE Divide!! • Drivers • Checkpoints Don’t divide!! Cell Cycle Checkpoints G2 Checkpoint • Is my DNA correctly replicated? Mitosis Checkpoint • Are chromosomes ready for separation? G1 Checkpoint/ Restriction Point • Is environment ok? • Is my DNA intact? Cyclin/Driver Function G1 Driver Cyclin D S Driver 1 S Driver 2 Cyclin E Cyclin A G2/M Driver Cyclin B Cell Signaling PDGF Outside PDGF Receptor Cytoplasm TP Transcription Factor Rb G1 driver gene Nucleus Cancer cells behave like stem cells … Specialization is normally a one way trip! Cancer cells Cancer cells lose their specialized functions … Genetic Changes - Mutated genes are expressed when they shouldn’t be. Epigenetic Changes – Genes expressed at the wrong time. Less Specialized Divides more More specialized Divides less Normal cells Cancer and Genetic/Epigenetic Mutations Oncogenes • Examples HER-2/neu (erbB-2): a growth factor receptor. ras: a signal transduction molecule myc: a transcription factor src: a protein tyrosine kinase. hTERT: an enzyme that functions in DNA replication. Bcl-2: a membrane associated protein that functions to prevent apoptosis. Tumor Suppressor Genes • Examples INK proteins p53 Rb BRCA1 BRCA2 APC p53 External signals: • Lack of Oxygen • Stress • Tissue Damage Internal signals: • DNA damage p53 Cell Cycle Arrest Apoptosis Mitochondria release ‘death’ proteins Apoptosis proteins open pore in mitochondria Apoptosis! ‘Die’ signals from p53 Once pore is open, it cannot be closed! Mitochondria Apoptosis, cont nucleus nucleus nucleus blebs • The cell blebs • Nucleus condenses blebs • Nucleus fragments • The blebs float away & are phagocytosed CANCER MODULE Units 3.1, 3.2, 3.3, 3.4, 4.2, 5.5 Human Genome Genes Exons Introns Intergenic DNA Regulatory sequences Transposons Other Transposons Cut ‘n’ paste Copy ‘n’ paste Cancer and Transposons • Transposons can interrupt a gene by jumping into it • Transposons have their own promoters. • So a transposon landing in front of a gene can turn ON the gene when it should be OFF! Transposon Gene Promoter Gene Transposon Cancer & Mutations Src Proto-oncogene/Tumor Suppressor Proto Oncogene c-Jun Proto Oncogene Deletion, Translocation PTEN Tumor Suppressor SNPs, Deletion p16 Tumor Suppressor SNPs, Deletion Ras Proto-Oncogene SNPs p27 Tumor Suppressor SNPs, Deletions Protein Most common mutation SNPs, Duplications Viruses & Cancer Inflammation & Cancer Wound Inflammatory signals Signals from the wound recruit immune cells Signals from immune cells start inflammation Immune cells secrete growth factors Signals stop when tissue repaired Chronic Inflammation & Cancer Damaged tissue Inflammation ROS Growth factors Rapid proliferation of mutating cells Chronic Inflammation, cont Fatty liver Acid reflux Stomach infection Cancer Metastasis • Cancer metastasis is like wound healing Stromal tissue is loosened Immune cells are recruited New blood vessels are made Immune cells and stromal cells signal epithelial cells to replicate. Cancer Treatments
