Thank you, Revati Masilamani! 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 Table Quiz Block, 2/22 – Mon, 2/27 3.1 – 3.4, 4.2, 5.5 Cancer Metastasis & Treatment Tue 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 Benign tumor Malignant tumor Metastasis

CANCER MODULE Units 1.3, 2.2, 2.3, 2.4, 2.5

REGULATION OF THE CELL CYCLE Divide!! Don’t divide!! Drivers Checkpoints

Cell Cycle Checkpoints G2 Checkpoint Is my DNA correctly replicated? Are chromosomes ready for separation? Mitosis Checkpoint Is environment ok? Is my DNA intact? G1 Checkpoint/ Restriction Point

Cyclin/Driver Function G1 Driver Cyclin D S Driver 1 Cyclin E S Driver 2 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! Normal cells Cancer cells More specialized Divides less Less Specialized Divides more 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.

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 Apoptosis! ‘Die’ signals from p53 Apoptosis proteins open pore in mitochondria ‘Die’ signals from p53 Mitochondria release ‘death’ proteins Apoptosis! Once pore is open, it cannot be closed! Mitochondria

Apoptosis, cont The cell blebs Nucleus condenses 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 Intergenic DNA

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

Proto-oncogene/Tumor Suppressor Cancer & Mutations Protein Proto-oncogene/Tumor Suppressor Most common mutation Src Proto Oncogene SNPs, Duplications c-Jun Deletion, Translocation PTEN Tumor Suppressor SNPs, Deletion p16 Ras Proto-Oncogene SNPs p27 SNPs, Deletions Simplified

Viruses & Cancer

Inflammation & Cancer Inflammatory signals Wound Signals from the wound recruit immune cells Signals from immune cells start inflammation Modified this slide for clarity Added the word scab, since this is post blood clotting Also since I couldn’t animate the slide ( it came from the internet), I added the arrow to show the drection of the green signals, and also added in the blue signals to show that they are secreted by the immune cells that are recruited. Also added the legend on the side Immune cells secrete growth factors Signals stop when tissue repaired

Chronic Inflammation & Cancer Damaged tissue Inflammation ROS Growth factors Added this slide to explain the role of a mutagenic plus pro-growth environment. Had drawn this kind of flow chart to explain the idea to Aimee (because the students were confused, thinking that oxidative stress leads to more proliferation, which is not true) She then used the same flowchart with them and it helped. 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