Cancer— The disease that results when The Cell cycle is unregulated at cell cycle checkpoints.

Cell cycle checkpoints-- Times during the cell cycle when cell cycle regulatory genes check for DNA defects or DNA sorting problems or other major cell defects). two kinds of cell cycle checkpoint regulator Proteins oncogenes—make cell divide too often tumor suppressors—prevents cell suicide of cells with defects; cell suicide is called apoptosis.

Why does it matter when a cell divides? Multicellular organisms are made of many kinds of cells which each carry out specialized jobs in the body. If there are too many of some and too few of others, then there is an imbalance in the body—failure of homeostasis. The extra cells use up resources and space, and they don’t do the jobs of the cells they replace.

For example, a human body has 220+ kinds of cells that must cooperate for homeostasis. Tissues Organs Organ systems 4

Cancer What is it? What causes it? Why does it make you sick? How can you cure it? 1/ BE1-8D7C962C04A5&blnFromSearch=1&productcode=US start at minute 8 lecture 1

cancer The disease resulting when some cells of the body divide too often or fail to die when DNA is seriously defective, broken, or incomplete Because there are too few of some types of cells and too many of others, homeostasis is lost.

219 /220 human cell types contain identical genomes. How is this possible? Simplified summary: Signal transduction mediated Gene expression. Starts before conception. Ends after death. 7

So, developing normally and continuing to have normal health depends on the body having the right numbers of every kind of cell, correct cell locations, and having every cell doing it’s correct job in cooperation with all the other 219 kinds of cells of the body.

If any one of the human cell types is too abundant or too scare relative to the others, functions of the body become imbalanced with each other. For example: too many thyroid hormone producing cells 9 Anxiety Breast enlargement in men (possible) Difficulty concentrating Double vision Eyeballs that stick out (exophthalmos) Eye irritation and tearing Fatigue Frequent bowel movements GoiterGoiter (possible) Heat intolerance Increased appetite Increased sweating Insomnia Menstrual irregularities in women Muscle weakness Nervousness Rapid or irregular heartbeat (palpitations or arrhythmia) Restlessness and difficulty sleeping Shortness of breath with exertion Tremor Weight loss (rarely, weight gain)

e.g., pheochromocytoma—cancer of the gland that produces adrenaline: symptoms of “fight or flight” response sweating rapid heart beat high blood pressure

e.g., too many growth hormone producing cells in pituitary gland—acromegaly if tumor is benign hand, foot, face, or tongue growth carpal tunnel syndrome joint and bone aches gigantism

Too few of a particular kind of cell causes problems.

Fetal alcohol syndrome

Progeria—premature aging—too few cell divisions

Normally cells divide only when signaled by molecules from other cells. These signals are called growth factors

Why do you get Cancer? Cell cycle protein coding genes or tumor suppressor genes become mutated so that cells divide out of sync with the needs of the entire body. The cells divide even after failing a checkpoint. Any one mutated to be active independent of the others can cause cancer. The rectangles show time of action of just a few of the oncogenes and tumor suppressor checkpoint proteins. 16

Melanoma skin cancer is an example of how cancer occurs if normal regulation of the cell cycle is disrupted. Melanoma is one type of skin cancer, developing when the pigmented cells in skin have mutations in cell cycle or tumor suppressor genes. 1ADE-466B-8C58-7F492883A4A4 1ADE-466B-8C58-7F492883A4A4 17

Proteins mutated to stimulate inappropriate cell division are called oncogenes. The study of cancer is called oncology. Oncogenes are mutated forms of proteins needed for normal cell division Carcinogens: Agents that cause mutations in oncogenes. Side effects of chemotherapy (use of drugs to kill cancer cells) occur because drugs that target oncogenes also interrupt actions of the normal versions of the proteins, killing or preventing normal cells..

Side effects of cancer drug treatments that target both oncogenes & proto-oncogenes in rapidly dividing normal cells Anemia Hair loss Diarrhea & nausea Weakened immune responses

Steps in cancer development 1) loss of normal cell cycle inhibition due to mutation in a gene coding an oncogene OR a tumor suppressor gene. Slowly growing clumps called BENIGN—harmless--polyps or tags. Moles additional mutations OF OTHER ONCOGENES OR TUMOR SUPPRESSOR GENES may cause cancer 20

Cell cycle checkpoint—time in the cell cycle when normal versions of oncogenes and tumor suppressors act to prevent abnormal cells from dividing. Apoptosis—programmed cell death by suicide of cells whose cell cycle checkpoint proteins have detected failure.

22 Stage 2 A mutation in at least 2 different cell cycle CONTROL genes tumors divide faster, may form large clumps, but they don’t spread.

Stage 3. Even more mutations in cell cycle regulatory genes occur—cells become malignant. But, they haven’t yet traveled farther than the lymph nodes nearest the tumor. Metastasis ---spreading of tumor cells. 23

How cancer cells travel: In circulating body fluids. nova/cancer/media/2805_0 6q.html

Stage 4. The cells divide rapidly without DNA proofreading, so mutations accumulate rapidly. The cells become nonfunctional and more and more defective, and they spread far from the original tumor, killing cells of the new location. 25

Heredity tendencies for families to have a higher than typical rate of a cancer type is due to mutations in one copy of a tumor suppressor gene. Both copies of the gene are mutated in people who eventually develop cancer. Not all members will experience the second mutation. But these people are twice as likely to have BOTH MUTATED as people not inheriting one defective tumor suppressor gene.

Cancers are named for their sites of origin. Carcinoma—arises in coverings or linings Sarcoma—begins in connective tissue (like tendons, ligaments, fat) Adenoma—arises in glands Glioma-arises in support cells of the brain Neuroma-arises in neurons Leukemia—arises in white blood cell precursors Etc.

Treatments: Remove tumors (sometimes chemotherapy is used before this to kill loose cells) Chemotherapy—use drugs to kill rapidly dividing cells OR to kill cells with a particular defective oncogene or tumor suppressor gene Radiation therapy—induce death of tumor cells by inducing major DNA breakage Immune therapy—inject extracts of the person’s tumor cells to induce immune response against the mutated, foreign proteins

The best defense against cancer: Early detection and treatment Regular check-ups Self checks for areas like breast and testicles (very common cancer sites) and moles or other areas if family history merits Awareness of changes in your body like blood in feces or new pain, blurred vision, etc Knowing family medical history of cancers to know what sites need most thorough checking or chemical tests (for early cancer protein markers) Avoiding exposure to carcinogens like cigarette or marijuana smoke or intense sunlight or radioactive materials

2. What is the general name of any gene that codes a protein normally involved in controlling progression through the cell cycle? 1.Proliferation gene 2.Growth factor gene 3.Proto-oncogene 4.Tumor suppressor gene 5.Oncogene 30

3. Mutations in tumor suppressor genes cause cancer if they are “loss of function” (recessive) mutations because these proteins are needed to initiate death of defective cells. 1.True 2.False 31

4. Mutations in proto-oncogenes cause cancer if they are “loss of function” (recessive) mutations since these increase likelihood cells will divide. 1.True 2.False 32

5. One role of a tumor suppressor gene is to induce apoptosis (cell suicide) when cells have major errors in DNA, preventing their entry into prophase. 1.true 2.false 33

6. Another name for apoptosis is cell suicide. It is initiated in the mitochondria. 1.true 2.false 34

7. Malignant tumors are more dangerous than benign tumors because: 1.Their cells are immortal 2.Their cells are not contact inhibited 3.Their cells are not density dependent 4.Their cells have mutated proto-oncogenes 5.Their cells can enter the lymphatic system or blood stream 35