Unit 2: Cancer and Unit 3: Genetics & DNA Biology

Cancer

Cancer

• Body is unable to control the division of cells

• Cancerous cells divide uncontrollably and interfere with normal physiology

• Don’t do their job within the body, stop non-cancerous cells from doing their job

Types of Cancers

Name of cancer reveals which organ or type of cell in which the cancer originated

Melanoma

Skin Pigment Cells

Leukemia

White blood cells in the bone marrow

Carcinoma

Lining of the internal organs or skin

Sarcoma

Connective tissue, such as bone

Lymphoma

Cells and tissues of the immune system

Risk of Cancer in Females

Risk of Cancer in Males

Smoking Rates

Life Processes Energy

Obtain and use energy from the environment

Life Reproduces, Grows, and Develops

• All living organisms have genetic material and reproduce

• Growth and development is determined by genetic composition of the organism

• Development often heavily influenced by environment

Life is Sensitive to Stimuli

• Sensitivity or response to stimuli

• Example—move toward or away from light or sound

Life is Capable of Regulation

Homeostasis: maintain internal environment (pH, water, temperature, etc.)

Life Adapts

• As an environment changes, natural selection causes the characteristics of a population to track those changes

• Ex: As the earth gets warmer due to global climate change, populations of organisms will slowly change such that they are better suited to warmer temperatures

Eukaryotic Cells & Membrane Bound Organelles

Membrane-bound compartments inside cells with specific functions

Nucleus

Ribosomes

• Make proteins

• All prokaryotic and eukaryotic cells have ribosomes

Cytoskeleton

• Provides shape and support

• Controls intracellular traffic and enables movement

Lysosomes

Endomembrane system
(EMS)

Composed of:

• Rough Endoplasmic Reticulum (RER)

• Smooth Endoplasmic Reticulum (SER)

• Golgi Apparatus

Function:

• Produce and modify molecules for export to other parts of the organism

• Break down toxic chemicals and cellular-by products

Cell Specialization

• All cells in an individual have the same DNA

• Cells only express the DNA they need to do their specialized job

Gene Expression

• Each cell has specific instructions about which genes to express and how much of that protein to produce

• Cancer cells ignore these instructions

Stage 1: Transcription

• DNA molecule is used as template to make an RNA molecule

• Happens in nucleus

• Central Dogma

• Messenger RNA (mRNA)

• RNA moves from nucleus to cytoplasm of the cell through nuclear pore

Stage 2: Translation

• Takes place on a ribosome

• Read by tRNA (anticodon) complimentary to mRNA

• GGU + CCA, AGA + UCU, ACC + UGG

• mRNA molecule used as a template to make protein

• Every three bases is a “codon” used to identify which amino acid to place next in the peptide chain

Recall: Protein Structure

• Order of amino acids determines all four levels of protein structures

• Structure determines function

• Mutations (or mistakes made during transcription or translation) can mean a non-functioning protein

Enzyme Pathways

• Most cellular processes require many different enzymes

• Even one non-functioning enzyme blocks the pathway

• Cancer occurs when the pathway in question relates to cell division

Human
Metabolism

The Cell Cycle P. 1

The Cell Cycle P. 2

• Interphase

• G1 (Gap/Growth 1): Cell grows

• S (Synthesis): DNA replicates

• G2 (Gap/Growth 2): Cell grows more

• Mitotic phase

• Mitosis: Copied chromosomes are moved into daughter cells

• Cytokinesis: Cell divides into two daughter cells

Cell cycle: Interphase 
G1 (Gap/growth 1) Phase

• Little visible change to cell

• Saves up energy

• Accumulates building blocks for DNA and proteins

• Cell growth and organelle duplication

Cell cycle: Interphase 
G0 Phase

• Inactive stage

• Cells are not actively preparing to divide

• Normal cell function

Cell cycle: Interphase 
S (Synthesis) Phase

• DNA replicates -Forms two identical copies of each chromosome (sister chromatids) attached at centromeres

• Uses Energy

Homologues and Sister Chromatids

Telomeres

• Ends of chromosomes, do not contain protein-coding DNA

• Get shorter every time the chromosome is replicated

• Once too short, cell undergoes apoptosis

• Telomerase: Enzyme that lengthens telomeres

• Present in cancerous cells, preventing cell death

Cell cycle: Interphase 
G2 (Gap/Growth 2) Phase

• Preparation for mitosis

• Cell replenishes energy

• Cytoskeleton is dismantled

• Cell growth

Cell cycle: mitotic phase P. 1

The parent cell’s nucleus, with its duplicated chromosomes, divides.

Cell Cycle: mitotic phase P. 2

• Mitosis is divided into a series of steps

• Remember: I.P.M.A.T.

Centriole

Organelles that make the spindle fibers out of microtubules

Spindle Fibers

Organize chromosomes during cell division, split them evenly between daughter cells

Prophase

• “First Phase”

• Nuclear envelope disappears: Provides access to the chromosomes

• Nucleolus disappears

• Where ribosomes are made

• Sister Chromatids coil slightly and attach to mitotic spindles at the centromere

Metaphase

Chromosomes are aligned in a middle plane called the metaphase plate

Anaphase

• Sister chromatids are split apart at the centromere

• Each side of the cell gets one set of homologues (one from dad’s genes and one from mom’s genes)

• Cell becomes elongated

Telophase

• Events are reversed to make two cells

• Chromosomes reach opposite poles and unravel

• Mitotic spindles are broken down into monomers that will be used to assemble new cytoskeletons

• Nuclear envelopes form around chromosomes

Cytokinesis P. 1

• The second part of the mitotic phase

• Physical separation of the cytoplasmic components into two daughter cells

Cytokinesis P. 2

• A ring of actin fibers forms and contracts around edge of division

• Contracts and splits cytoplasms of cells until they are separate

Cell cycle in normal cells: Checkpoints

• The cell cycle has checkpoints to control division

• Regulate speed at which cell goes through cycle

• Ensure cell is ready for division

• Prevents compromised cells from continuing to divide

• Cells that fail checkpoints go to G0 stage or undergo apoptosis (cell death)

Cell cycle control system:
 G1 Checkpoint

• Checks for adequate cell size and energy reserves

• Checks DNA for damage

• Important for cancer prevention

Cell cycle control system
: G2 Checkpoint

• Checks for adequate cell size and protein reserves

• Checks for complete chromosome replication and DNA damage

Cell cycle control system
: M checkpoint

• Checks to ensure chromatids are ready for division

• If a cell does not meet all the requirements at each checkpoint, it will not progress to the next stage of the cell cycle.

Why Certain Mutations Lead to Cancer

• Mutation: Permanent changes to DNA

• Causes of Cancer-Causing Mutations 1. Genetics: Several kinds of genes known to increase risk of cancer 2. Environment: Radiation, Chemicals, Viruses 3. Chance: DNA Replication Error

Mutations

Tumor-Suppressor Genes

• Genes that code for proteins that examine DNA for damage at G1 checkpoint

• STOP/SLOW cell cycle when functioning properly

• Need one functioning copy of TS gene to work

• If you inherit a malfunctioning allele, one mutation leaves you without a TS gene in that cell

P53 tumor-suppressor gene

• Activates DNA repair enzymes

• Stops cell cycle and places cell in G0 phase

• Promotes apoptosis in unrepairable cells

• 50% of cancers are p53 mutations

BRCA1 tumor-suppressor gene

• Protein active at G1 checkpoint

• Inspects DNA for strand breaks (also sends cells to G0).

• Mutated copy causes breast/uterine cancers in women, prostate cancer in men

Proto-oncogenes

• Speed up cell cycle by being overly sensitive to extracellular signals (or not needing them at all for activation)

• One mutated copy is enough to create issues

ERBB2 Proto-Oncogene

• Healthy version produces HER-2 Protein

• Surface receptor protein that regulates cell growth/repair in surface lining tissues

• 25% of breast cancers involve overexpression (too much protein) from this gene

Characteristics of Cancer Cells 
1. Different Appearance

Cancerous cells are odd shapes, with larger nuclei that stain darker when looked at under a microscope

Characteristics of Cancer Cells 
2. Unlimited Cell division

• Normal cells can divide a finite number of times

• Cancer cells never lose their ability to divide

Characteristics of Cancer Cells
 3. Less specialization

• Mutations cause cells to stop expressing the correct proteins, losing function and specialization

• Tumor: Mass of cells

Characteristics of Cancer Cells 
4. changes to blood flow

• Angiogenesis: Tumor releases growth factors, triggering nearby capillaries to grow toward the tumor

Characteristics of Cancer Cells
 5. invade surrounding tissues

Characteristics of Cancer Cells 
6. Move to other parts of the body

• Metastasis: Cancer cells separate from a tumor and spread throughout the body via the circulatory or lymphatic systems

• White cells in this photo are cancerous

Cancer Progression

• Organized in Stages

• Stage determined by:

• Size of tumor

• Whether tumor has invaded nearby tissues

• Whether cancer cells have spread to lymph nodes

• Whether cancer cells are present in other organ tissues

Stage 0, 1 Cancer

• Tumor is limited to a very small area

• Only lymph nodes very close to tissue have cancer cells (if any lymph nodes are involved at all)

Stage 2 Cancer

• Tumor is larger and more invasive to surrounding tissues

• Still entirely within its originating tissue though

• Lymph nodes may have cancer cells in them

Stage 3 Cancer

• Tumor is larger and moved out of originating tissues, but not to distant organs

• Cancer cells detectable in lymph node tissues

Stage 4 Cancer

Cancer is detectable in distant tissues outside originating area

Homeostasis

• Constant internal conditions maintained by body systems

• Temperature, pH, salt level, water level, blood sugar

• Maintained by negative feedback loops

Negative Feedback Loop

1. Body senses abnormal condition

2. Body sends signals to control system

3. Body responds

4. Body returns to normal

5. Original signal stops

Water and Salt Balance

• Kidney collects and filters fluids

• Removes waste and regulates water/salt concentration in blood

• When water is high: less water conservation (you pee more)

• When water is low: more water conservation (you pee less)

Blood Sugar Balance

• Pancreas regulates blood sugar levels

• When blood sugar is high: Releases insulin

• When blood sugar is low: Releases glucagon

Diabetes

• Can’t regulate blood sugar

• Blood sugar can go to dangerously high levels

• Type I: Pancreas doesn’t make enough insulin

• Type II: Cells are insensitive to insulin

Endocrine System

• System of glands that secrete hormones to maintain homeostasis

• Hormones: Chemicals that travel through blood and cause cellular responses in distant tissues

Hormones & 
Feedback Loops

• Hormones almost always function in negative feedback loops

• Why?

• Can you think of a time when a positive feedback loop would be needed?

Cancer Disrupts Homeostasis

• Tumors interfere with chemical signals

• Prevent release by organs

• Prevent transmission by blocking blood/lymphatic vessels

• Prevent sense organs from detecting abnormal condition

• Prevent target organ from responding to signal

Cancer alters body chemistry

• Bone cancer makes regulating blood calcium more difficult

• High blood calcium is dangerous

• Liver cancer makes it hard to produce enzymes needed for digestion and blood sugar regulation

Cancer disrupts organ function

• Tumors disrupts oxygen flow to organs, take away other resources

• Tumors put pressure on parts of the brain that regulate important behaviors like breathing

Treating Cancer

1. Diagnosis and Stage Determination

2. Treatment Protocol

• Chemotherapy

• Radiation

• New Treatments

1. Diagnosis: Genetic Testing

DNA test for known cancer-causing alleles

1. Diagnosis: Blood Tests

• Number of white blood cells in blood

• More WBCs means immune response

• Tumor cells in blood if cancer is stage 4

• Blood chemistry changes caused by cancer disrupting tissues

• Calcium, enzymes, ions

• Presence of cancer produced proteins

1. Diagnosis: Body Scans

• Breast Cancer: Mammogram

• Other scans: CT Scans, PET Scans, MRIs

3. Treatment: Chemotherapy

• Using drugs to kill (or just stop division) in cancer cells

• Drugs injected that interfere with cell cycle, which affects rapidly dividing cells more than others

• Drawback: Many side effects because drugs affect all cells

Chemotherapy: Alkylating Agents

• Integrate into DNA, causing breaks in the strands

• Side Effects: Leukemia

Chemotherapy: Topoisomerase Inhibitors

Disable topoisomerase enzyme, which unwinds DNA during replication

Chemotherapy: Antimetabolites

• Mimic nucleotides and can be integrated into DNA molecules

• Can’t work with DNA replication enzymes, preventing cell division

Chemotherapy: Alkaloids & Taxanes

• Block spindle fiber formation or breakdown (prevents cell division from starting or ending)

• Naturally produced by plants

• Drawbacks: Nerve damage

3. Treatment: Radiation

• Movement of energy in waves or particles

• Shorter wavelengths have more energy

Radiation Therapy

• Damages DNA within a cell, which slows or stops cell division

• Target specific tumor sites

• Less effective for metastatic cancers

3. Treatment:
 Future of Treatments

1. Immunotherapy

• Use the body’s immune system to attack tumors

2. Genome Editing

• Remove and replace cancer-causing genes

Gene

• Unit of DNA that determines a trait

• Infinite # of traits

• Phenotype: physical trait

• Produces a protein, RNA

• Genes interact with each other and the organism’s environment to determine final trait

• Genes AND environment determine the traits

Inheritance

• Genes are inherited via sexual reproduction

• Males produce sperm, females produce eggs

• Fusion of these gametes produces genetically distinct offspring

Genetic Disease

• Disease caused by mutation in DNA that is passed from parent to offspring

• Ex: Sickle-Cell Anemia, Cystic Fibrosis

Sickle-Cell Disease P. 1

• Mutation in gene that codes for protein (Hemoglobin) on red blood cells (RBCs) changes shape of RBCs from concave disc to a sickle

• Sickle-cell shape leads to myriad health problems caused by low access to oxygen

• Alters transport of ions, osmotic pressure

• RBCs have millions of hemoglobin molecules on the surface to carry oxygen, so sickle cells do not bind enough oxygen

Sickle-Cell Disease P. 2

• Good trait for Studying Genetic Disease:

1. Single mutation leads to Sickle-Cell Disease (inheritance is straightforward)

2. Low incidence of genetic interactions changing the effect of the disease

3. Relatively free from environmental influence

• Polygenic: influenced by two or more genes

Red Blood Cells (RBCs)

• Deliver and exchange gases to body tissues

• Lack a nucleus, which makes the cell concave in shape and increases surface area for oxygen transfer

Hemoglobin

• Cell without a nucleus

• Protein complex composed of four polypeptide chains (globins, each globin produced by a different gene)

• Four polypeptides each have a heme group with an iron (Fe) atom

• O2 binds to Fe

• Up to 250 million hemoglobin molecules per RBC

Circulatory System

• Heart pumps blood around body in blood vessels to transfer oxygen to tissues

• Arteries: Vessels where blood is moving away from heart

• Veins: Vessels where blood is moving toward the heart (carry both deoxygenated and oxygenated blood)

Heart Structure

• Humans have four chambered hearts

• Top: Atria (singular: Atrium)

• Bottom: Ventricles (have more muscle)

• Right side: Deoxygenated blood

• Left Side: Oxygenated blood

Blood Pathway Through Heart

1. Deoxygenated blood enters right atrium on return from body.

2. Deoxygenated blood Enters right ventricle.

3. Deoxygenated blood is pumped to the lungs

4. Oxygenated blood returns to left atrium from lungs.

5. Oxygenated blood Enters left ventricle.

6. Oxygenated blood is pumped through the Aorta to body from left ventricle.