Cell Division Meiosis Cell Division Meiosis Abnormal Meiosis.
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Transcript of Lecture 7: Cell Division and Cancer Objectives: Understand basic concepts of cancer Understand cell...
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Lecture 7: Cell Division and CancerLecture 7: Cell Division and Cancer
Objectives:
Understand basic concepts of cancer
Understand cell division
Understand how cell division is regulated
Understand programmed cell death
Key Terms: Mitosis, interphase, tumor, metastasis, angiogenesis, neoplasm, benign, malignant, adenoma, carcinoma, tumor suppressor, growth factor, check point, oncogene, programmed cell death
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Leading Causes of Death
Total US Population• Heart Disease• Cancer• Stroke• Lung diseases• Accidents• Diabetes• Flu and Pneumonia• Alzheimer's disease• Kidney Disease• Infections
(Most current data available are for U.S. in 2001) www.cdc.gov/nchs/fastats/lcod.htm
US Population 20-24 • Accidents• Homicide • Suicide• Cancer • Heart disease • Genetic Disease• HIV (AIDS)• Stroke • Flu and Pneumonia
• Diabetes
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Leading Sites of New Cancer and Deaths 2003 estimates
Male New cases DeathsProstate220,900 28,900Lung 91,800 88,400Colon 72,800 28,300Bladder 42,200 8,600Melanoma (skin) 29,900 na
Female New cases DeathsBreast 211,300 39,800Lung 80,100 68,800Colon 74,700 28,800Uterine 40,100 6,800Ovary 24,400 14,300
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Cancer
Features of Cancer Cells
1. Make their own growth signals
2. Insensitive to growth stopping signals
3. Insensitive to self destruct signals
4. Immortal ! : unlimited replication
5. Stimulate new blood vessel growth
6. Invasive : move out of tumor
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How does Cancer Start?Cellular Damage Control
Normal cells protect their DNA Information
Damage control system
1. Detect DNA and cellular damage
2. Stop cell division (prevent replication of damage)
3. Activate damage repair systems
4. Activate self destruct system
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DAMAGEEVENT
Stop Cell DivisionActivate Damage RepairDamage Assessment
Repair is Successful
Mild to Moderate DamageSevere
Damage
Programmed Cell Death
RepairFails
Damage AccumulationLeads to Cancer
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Tumor
• An abnormal mass of undifferentiated cells
• It often interferes with body functions
• It can absorb nutrients needed elsewhere
• It can be benign, grow slowly and stay in one area.
• It can be malignant, grow rapidly and spread to other parts of the body
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Cancer Terminology• Neoplasm-Cells that have no potential to spread to and
grow in another location in the body
• Benign-Non-cancerous growth that does not invade nearby tissue or spread
• Malignant-growth no longer under normal growth control
• Metastasis-spread of cancer from its original site to another part of the body
• Adenoma-A benign tumor that develops from glandular tissue
• Carcinoma-A tumor that develops from epithelial cells, such as the inside of the cheek or the lining of the intestine
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Understanding Cancer
To understand cancer, you must understand three fundamental cellular processes
1.Cell Division2. Gene Regulation
3. Programmed Cell Death
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Cell Division
Key concepts of Cell Division
1. Cell Cycle
2. DNA Replication
3. Chromosome Division
4. Cell Division
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Cell Division
Key Concept:
There are two types of cell division
Mitosis – for growing, results in two identical cells.
Meiosis – for sexual reproduction, results in four cells with only one copy of chromosomes
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Cell Cycle
• Cycle starts when a new cell forms• During cycle, cell increases in mass
and duplicates its chromosomes• Cycle ends when the new cell divides
Key Terms:Cell Cycle, Chromosomes, Cell Division
What do they Mean?
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Fig. 8.4, p. 130
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Interphase: Phase between division and starting division again.Three parts of Interphase1. G1 1st Growth phase- cell makes parts, and does normal
things2. S Synthesis phase- DNA replication3. G2 2nd Growth phase- making parts for cell division
4. G0 Zero Growth phase• Like getting stuck in park• Terminal development
Key Concept:At each step, the cell must
be in orderLongest part of the cycleCell mass increasesCytoplasmic components doubleDNA is duplicated
Decoding the Cell Cycle
G1 S
INTERPHASE
G2
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Control of the Cycle
• Once S begins, the cycle automatically runs through G2 and mitosis
• The cycle has a built-in molecular brake in G1 (p53 tumor suppressor)
• Cancer involves a loss of control over the cycle, malfunction of the “brakes”
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Cell Division DNA Replication Summary
Enzymes• Topoisomerase unwinds strands• DNA Polymerase attaches new complementary nucleotides• DNA Ligase connects the bonds between phosphate sugar
backbone of the new nucleotidesChemical Bonds • Break hydrogen bonds with Topoisomerase• Make Hydrogen bonds with DNA Polymerase• Make covalent bonds with DNA LigaseFinal Products• The strand being replicated is the template• Start with one copy of a DNA molecule and end with two
copies– New copies have one new strand and one old strand– Both copies are “identical” to the original
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MIT
OS
IS
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Mitosis
Definition:
• Period of nuclear division
• Followed by cytoplasmic division
Multi-step process
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nucleusplasmamembrane
pair of centrioles
chromosomesnuclear envelope
CELL AT INTERPHASE EARLY PROPHASE LATE PROPHASE
TRANSITION TO METAPASE
Fig. 8.7a, p. 132
The cell duplicates its
DNA, prepares for
nuclear division
Mitosis begins. The DNA and its
associated proteins have started to
condense. The two chromosomes
color-coded purple were inherited
from the female parent. The other
two (blue) are their counterparts.,
inherited from the male parent.
Chromosomes continue to
condense. New
microtubules become
assembled. They move one
of the two pairs of centrioles
to the opposite end of the
cell. The nuclear envelope
starts to break up.
Now microtubules penentrate
the nuclear region. Collectively,
they form a bipolar spindle
apparatus. Many of the spindle
microtubules become attatched
to the two sister chromatids of
each chromosome.
MITOSIS
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METAPHASE ANAPHASE TELOPHASE INTERPHASE
Fig. 8.7b, p. 133
All chromosomes have become
lined up at the spindle equator.
At this stage of mitosis (and of
the cell cycle), they are most
tightly condensed
Attachments between the
two sister chromatids of each
chromosome break. The two
are separate chromosomes,
which microtubules move to
opposite spindle pores.
There are two clusters
of chromosomes, which
decondense. Patches of
new membrane fuse to form
a new nuclear envelope.
Mitosis is completed.
Now there are two
daughter cells. Each
is diploid; its nucleus
has two of each type
of chromosome, just
like the parent cell.
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Key Concept:
• During mitosis each cell gets a high fidelity copy of each chromosome
• Multiple check points prevent run-away cycling
Cancer cells are in run-away mode, the checkpoints are broken or ignored
Cell DivisionMitosis
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Stupmer also… Key Concept:
• Each chromosome has two strands of DNA
• Each chromosome has one copy of each gene*
• Each somatic cell has two of each chromosome
• Each somatic cell has two copies of each gene*
*assume single copy genes
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Chromosomes
DNA and proteinsarranged as cylindrical fiber
DNA
Histone
Nucleosome
Chromosome: A double stranded DNA molecule & attached proteins
Almost no naked DNA
Chromosome (unduplicated)
Chromosome (duplicated)
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Cancer and Genetics
• Genetic disease
• Meiosis
• Sexual reproduction
Focus on mechanism(Genetic Disease etc. after Exam #1)
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Understanding Cancer
To understand cancer, you must understand three fundamental cellular processes
1. Cell Division
2.Gene Regulation3. Programmed Cell Death
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Gene RegulationOncogenesGenes who’s products transform normal cells
into cancer cells.– Required for normal cell cycling– Products of these genes are no longer regulated – “gain of function”
Tumor suppressorsProteins that prevent the progression of the
cell cycle– P53 is a DNA binding protein that recognizes
damaged DNA and stops DNA replication– “loss of function”
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Gene Regulation
• Growth Factors– Signaling molecules that enhance cell division– Activate “cascade” of signaling inside cell– Hyperactive cascade members can trigger cell
division by turning genes on at the wrong time– Hyperactivity lets cells ignore regulatory signals
• Anchorage dependent cell cycle arrestAdhesion is required for normal cell division ratesCancer cells loose cell adhesion moleculesCancer cells don’t respond to limiting signals
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Gene RegulationImortalization
• Normal cells only divide about 50 times in a petri dish (if you can get them to divide)
• Cancer cells just keep dividing (HeLa and MCF-7 cells)
• Telomers (ends of chromosomes) usually spell the end for normal cells, but they don’t wear out
Angiogenesis
Blood vessel formation
Cancer cells trick blood vessels into supplying nutrients
Cancer cells secrete the growth factors that they are using
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Cancer and Smoking• The smoke emerging from a cigarette contains about 1010
particles/ml and 4800 chemical compounds
• There are over 60 carcinogens in cigarette smoke that have been evaluated for which there is 'sufficient evidence for carcinogenicity' in either laboratory animals or humans
• These compounds damage DNA in the cells of the lung. The mechanism behind the damage is unknown.
• Damage leads to mutations
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Smoking and Cancer• The kicker
– Somehow p53 gets more mutations than other randomly selected sites
– The mutations keep p53 from binding to DNA
– This means that p53 can no longer prevent DNA replication when there is other damage
x xxDNA
TranscriptionTranslation
p53
STOP
mp53
GO
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Understanding Cancer
To understand cancer, you must understand three fundamental cellular processes
1. Cell Division
2. Gene Regulation
3.Programmed Cell Death
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Programmed Cell Death
Key Concepts
• Cells are caused to die on purpose
– Two examples: Epithelial cells, Damaged cells
• Based on a balance of protecting proteins and killing proteins.
• Cancer cells often have high levels of protecting proteins.
AKA: Apoptosis
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Programmed Cell Death
The cell death program1. Activated by cell surface receptors
2. Makes pores in Mitochondria
3. DNA is chopped up
4. Blebbing (not popping)
5. Adsorption by neighbors
Nematodes, frog tails, webbed fingers, and HIV
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Programmed Cell DeathColon Cancer• Crypt
• Polyp
• Malignant polyp
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The Cancer has Spread
• Two linked processes
– Metastasis
– Angiogenesis
• Key concpet– Metastasized cancer cells require angiogenesis to
produce another malignant tumor– Angiogenesis- formation of new blood vessels– Metastasis- migration of cancer cells to a new location
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Metastasis
Cancer cells leave the tumor and establish new colonies in other tissues
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Angiogenesis
• Depends on growth factors released by the invading cancer cells
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Angiogenesis and Metastasis
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Angiogenesis and Metastasis
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Markers for Cancer
• Markers are proteins found in blood
• Levels markers correlates with certain cancer types
• Some tumor markers are antigens, others are enzymes.
• Example: prostate-specific antigen (PSA) is a marker for prostate cancer in males
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• Growing cells in culture allows researchers to investigate processes and test treatments without danger to patients
• Most cells cannot be grown in culture
Cancer Research
Henrietta Lacks
HeLa Cells
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HeLa Cells
• Line of human cancer cells that can be grown in culture
• Descendents of tumor cells from a woman named Henrietta Lacks
• Lacks died at 31, but her cells continue to live and divide in labs around the world
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ReviewReviewThursday in class reviewThursday in class review
Normal time and placeNormal time and place
Thursday evening reviewThursday evening review
Anthony Hall 1279Anthony Hall 12797:00 pm to 9:00 pm7:00 pm to 9:00 pm
Review Outline Available on Website Review Outline Available on Website Wednesday at about 4:00 pmWednesday at about 4:00 pm
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EXTRA CREDIT #1
• Please stay after class for topic assignments
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Question #1Question #1
Energy for metabolic processes only Energy for metabolic processes only comes from Sugar comes from Sugar
A. TrueA. True
B. FalseB. False
19%19%
81%81%
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Question #2Question #2
Cells burn insulin to make ATP Cells burn insulin to make ATP
A. TrueA. True
B. FalseB. False ?50%50%50%50%
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Question #3Question #3
More ATP is produced by the More ATP is produced by the electron transport system than electron transport system than is produced by glycolysis is produced by glycolysis
A TrueA True
B FalseB False
58%58%
42%42%?
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Question #4Question #4
• Is Insulin a: Is Insulin a:
A. Carbohydrate A. Carbohydrate
B. Protein B. Protein
C. Lipid C. Lipid
D. OrganophosphateD. Organophosphate
20%20%
33%33%
18%18%
29%29% ?
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Question #5Question #5
Carbon Dioxide Gas is used to build Carbon Dioxide Gas is used to build energy storage molecules in the liver energy storage molecules in the liver
A True A True
B FalseB False
30%30%
70%70%