Understanding Cancer Developed by: Lewis J. Kleinsmith, Ph.D., Donna Kerrigan, M.S., Jeanne Kelly, Brian Hollen Lesson Objectives: Illustrate what cancer is Explain the link between mitosis, genes that control mitosis, mutations and cancer Discover causes and risk factors

Decide with your partner

What Is Cancer? What is a good definition for cancer? Cancer - A disease in which abnormal cells divide uncontrollably and destroy body tissue (mayoclinic.com)

How Are Normal & Cancer Growth Different ? Cancer cell division Fourth or later mutation Third mutation Second mutation First mutation Uncontrolled growth Cell Suicide or Apoptosis Cell damage— no repair Normal cell division

Example of Normal Growth Cell migration Dermis Dividing cells in basal layer Dead cells shed from outer surface Epidermis

The Beginning of Cancerous Growth Underlying tissue During the development of skin cancer, the normal balance between cell division and cell loss is disrupted. The basal cells now divide faster than is needed to replenish the cells being shed from the surface of the skin.

Think – Pair – Share What is the difference between normal cell division and cancer cell division?

Tumors (Neoplasms) Underlying tissue The gradual increase in the number of dividing cells creates a growing mass of tissue called a tumor (neoplasm)

HORSES Explain to your partner how a tumor is formed.

Invasion and Metastasis 3 Cancer cells reinvade and grow at new location 1 Cancer cells invade surrounding tissues and blood vessels 2 Cancer cells are transported by the circulatory system to distant sites

Malignant versus Benign Tumors Malignant (cancer) cells invade neighboring tissues, enter blood vessels, and metastasize to different sites Time Benign (not cancer) tumor cells grow only locally and cannot spread by invasion or metastasis

Why Are Malignant Tumors Dangerous? Melanoma cells travel through bloodstream Melanoma (initial tumor) Brain Liver

Different Kinds of Cancer Cancer can originate almost anywhere in the body Lung Breast (women) Colon Bladder Prostate (men) Some common sarcomas: Fat Bone Muscle Lymphomas: Lymph nodes Leukemias: Bloodstream Some common carcinomas:

Naming Cancers PrefixMeaning adeno-gland chondro-cartilage erythro-red blood cell hemangio-blood vessels hepato-liver lipo-fat lympho-lymphocyte melano-pigment cell myelo-bone marrow myo-muscle osteo-bone Cancer Prefixes Point to Location

Dogs Tell your partner where the cancer, myeloma, will be located.

Horses Tell your partner where the cancer, osteosarcoma, will be located.

Genes and Cancer

Checkpoint Normal Vs. Cancerous Cell Growth

What happens to genes to cause cancer? Chromosomes are DNA molecules Heredity Radiation Chemicals Viruses

DNA Structure DNA molecule Chemical bases G C T A

THINK – PAIR - SHARE What are the 3 different types of mutations possible for DNA?

DNA Mutations Additions Deletions Normal gene Single base change DNA C T AGCGAACTAC AGGCGCTAACACT AGCTAACTAC AGAACTAC

Groups of Genes Linked to Cancer 2 main groups: Proto – Oncogenes and Oncogenes Tumor suppressor genes Sometimes: DNA repair genes

Proto-Oncogenes and Oncogenes Mutated/damaged = oncogene Oncogenes accelerate cell growth and division Cancer cell Normal cell Normal genes regulate cell growth Proto-Oncogenes – genes that, when damaged, could lead to cancer - Typically function to stimulate cell division, inhibit cell differentiation & halt cell death (apoptosis) Oncogenes – damaged or mutated proto-oncogenes

Proto-Oncogenes and their role in cell growth / reproduction Receptor Normal Growth-Control Pathway DNA Cell proliferation Cell nucleus Transcription factors Signaling enzymes Growth factor

Oncogenes are Mutant Forms of Proto-Oncogenes Cell proliferation driven by internal oncogene signaling Transcription Activated gene regulatory protein Inactive intracellular signaling protein Signaling protein from active oncogene Inactive growth factor receptor

Tumor Suppressor Genes Normal genes prevent cancer Remove or inactivate tumor suppressor genes Mutated/inactivated tumor suppressor genes Damage to both genes leads to cancer Cancer cell Normal cell

Tumor Suppressor Genes Act Like a Brake Pedal Tumor Suppressor Gene Proteins DNA Cell nucleus Signaling enzymes Growth factor Receptor Transcription factors Cell proliferation Tumor Suppressor Genes - genes that instruct cells to produce proteins that restrain cell growth and division

Example: p53 Tumor Suppressor Protein Triggers Cell Suicide Normal cellCell suicide (Apoptosis) p53 protein Excessive DNA damage In cells that have undergone DNA damage, the p53 protein acts like a brake pedal to halt cell growth and division. If the damage cannot be repaired, the p53 protein eventually initiates cell suicide

DNA Repair Genes Cancer No cancer No DNA repair Normal DNA repair Base pair mismatch TCATC AGTCG TCAGC AGTCG AGTGAGTAG TCATCTCATC

Cancer Tends to Involve Multiple Mutations Malignant cells invade neighboring tissues, enter blood vessels, and metastasize to different sites More mutations, more genetic instability, metastatic disease Proto-oncogenes mutate to oncogenes Mutations inactivate DNA repair genes Cells proliferate Mutation inactivates suppressor gene Benign tumor cells grow only locally and cannot spread by invasion or metastasis Time

Mutations and Cancer Genes Implicated in Cancer

Cancer is a Progressive Disease Usually, many changes occur before cells grow out of control

Using your notes, write a paragraph that summarizes the process of how a cell changes from having normal cell growth and reproduction to cancerous cell growth in your class journal. You must include and underline all of the following terms: Proto-Oncogenes Oncogenes Tumor Suppressor Genes Apoptosis Cell Cycle Mutations Uncontrolled Growth Write a Summary Paragraph