Download Cancer PowerPoint

Cancer Biology and Cell Technology
Chapter 20
1
US Mortality, 2003
1.
Heart Diseases
No. of % of all
deaths deaths
685,089
28.0
2.
Cancer
556,902
22.7
3.
Cerebrovascular diseases
157,689
6.4
4.
Chronic lower respiratory diseases
126,382
5.2
5.
Accidents (Unintentional injuries)
109,277
4.5
6.
Diabetes mellitus
74,219
3.0
7.
Influenza and pneumonia
65,163
2.7
8.
Alzheimer disease
63,457
2.6
1.
Nephritis
42,453
1.7
10.
Septicemia
34,069
1.4
Rank Cause of Death
2
2006 Estimated US Cancer Cases*
Men
720,280
Women
679,510
Prostate
33%
31%
Breast
Lung & bronchus
13%
12%
Lung & bronchus
Colon & rectum
10%
11%
Colon & rectum
Urinary bladder
6%
6%
Uterine corpus
Melanoma of skin
5%
Non-Hodgkin
lymphoma
4%
Kidney
3%
3%
Thyroid
Oral cavity
3%
3%
Ovary
Leukemia
3%
2%
Urinary bladder
Pancreas
2%
2%
Pancreas
18%
22%
All Other Sites
All Other Sites
4%
4%
Non-Hodgkin
lymphoma
Melanoma of skin
*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.
Source: American Cancer Society, 2006.
3
2006 Estimated US Cancer Deaths*
Men
291,270
Women
273,560 26%
Lung & bronchus
31%
Colon & rectum
10%
15%
Breast
Prostate
9%
10%
Colon & rectum
Pancreas
6%
6%
Pancreas
Leukemia
4%
6%
Ovary
Liver & intrahepatic
bile duct
4%
4%
Leukemia
Esophagus
4%
3% Non-Hodgkin
lymphoma
Non-Hodgkin
lymphoma
3%
3%
Uterine corpus
2%
Multiple myeloma
Urinary bladder
3%
2%
Brain/ONS
Kidney
3%
All other sites
23%
23%
Lung & bronchus
All other sites
ONS=Other nervous system.
Source: American Cancer Society, 2006.
4
Overview of Genetic Recombination
•
Two types of recombination processes alter
genes.
– gene transfer - one chromosome or genome
donates a segment to another chromosome
or genome
– reciprocal recombination - two
chromosomes trade segments
5
Gene Transfer
•
•
•
What is a Plasmid?
– Found in prokaryotes
– Circular bit of DNA
– Extrachromosomal
– About 5% of bacterial DNA
What is a transposon?
– A DNA sequence capable of moving around
What is transposition?
– a random(?) movement of transposable
elemenes (genes) which results in genetic
recombination
6
Gene Transfer
•
•
Plasmid creation
– All cells have recombination enzymes that
can cause double duplexes to undergo
reciprocal exchange.
 loop is freed from rest of DNA and
becomes a plasmid
Integration
– Region of plasmid DNA involved in original
exchange, recognition site, aligns with
matching sequence on main genome.
7
Excision and Integration of a Plasmid
8
9
Gene Transfer
•
Conjugation
– Bacteria have genes encoding protein
subunits that assemble on the surface of
the bacterial cell, forming a pilus.
 rolling-circle replication
10
11
Gene Transfer
•
•
Transposition
– Transposons encode transposase enzyme that
inserts transposon into the genome at a random
site.
 causes insertional inactivation
 facilitates gene mobilization
– Transposition can rapidly generate composite
plasmids (resistance transfer factors).
 antibiotic resistance
How could transposition cause cancer?
12
Transposition
13
14
Mutations
•
What is a mutation?
– Mutations are changes in the hereditary
message of an organism.
15
Mutations
•
•
•
What is a mutation?
– Mutations are changes in the hereditary
message of an organism.
What kinds of mutations are most significant
in regards to heredity?
– Only mutations in the germ line (cells that
form gametes) are passed to subsequent
generations.
What is the difference between somatic cells
and germ-line cells?
16
Mutations
•
•
•
What is a mutation?
What kinds of mutations are most significant
in regards to heredity?
– Only mutations in the germ line (cells that
form gametes) are passed to subsequent
generations.
What is the difference between somatic cells
and germ-line cells?
– Somatic cells are normal body cells and
germ line cells are sex cells.
17
Mutations
•
•
Mutations in somatic cells may have a large
effect on the individual, as they are passed
on to other cells in the same individual.
Why is this so?
18
Mutations Altering DNA
Sequence
•
•
•
•
•
Base substitution
Chemical modification
DNA breaks
Slipped mispairing
Triplet expansion
19
20
Mutations Arising from Gene Position Changes
•
Chromosomal rearrangement
– translocations - segments of one
chromosome become part of another
chromosome
– inversions - orientation of a portion of
chromosome is reversed
– aneuploidy - genes or chromosome
segments are added or deleted
– polyploidy - entire sets of chromosomes
added
21
Consequences of Inversion
22
23
Mutations Arising from Gene Position Changes
•
Insertional inactivation
– Transposons are capable of moving to
different locations in the genome.
 select new locations at random
 may cause insertional inactivation
24
DNA Repair
•
•
•
•
Mismatch repair - locate replication errors and
correct daughter (non-methylated) strand
– Where have we heard of methylated DNA
before?
– dam mutations (deficient in adenine methylation)
Specific repair systems
– UVR photorepair system animation
– Uracil-N-glycosylase
Excision repair Post-replication repair 25
•
•
•
•
•
DNA Repair
Mismatch repair Specific repair systems
Excision repair - excise damaged region and
fill in gap using repair polymerase
– Non specific
Post-replication repair
– Can handle double stranded DNA breaks
– recombinational repair
Why talk about DNA Repair mechanisms in
a chapter about Cancer?
26
What is Cancer?
•
Cancer is a growth disorder of cells.
– uncontrolled and invasive growth
 results in tumor
 may metastasize
– can be caused by mutagenic chemicals or
possibly viruses
 cell division never stops in a cancerous
line, and are thus essentially immortal
27
What is Cancer? – Fig 20.11
Carcinoma of the lung
Connective
tissue
Blood
vessel
Lymphatic
vessel
Smooth
muscle
Metastatic cells
Blood vessel
28
Causes of Cancer
•
•
Sarcomas - arise in connective tissue or
muscle
Carcinomas - arise in epithelial tissue
– Carcinogens are agents thought to cause
cancer.
 Ames test
– Carcinogenic chemicals are all mutagenic.
29
What is epithelial tissue?
Structure
•
•
•
•
•
•
covers the whole surface of the body.
cells closely packed and ranged in one or more
layers.
tissue is specialized to form the covering or lining of all
internal and external body surfaces.
Epithelial tissue that occurs on surfaces on the interior
of the body is known as endothelium.
cells are packed tightly together, with almost no
intercellular spaces and only a small amount of
intercellular substance.
usually separated from the underlying tissue by a thin
sheet of connective tissue; basement membrane.
30
Causes of Cancer – (Data from 2002)
31
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Causes of Cancer – Ames Test
Count the
number of
bacterial
colonies
that grow
Suspected
carcinogen
Mix
Histidinedependent
bacteria
Pour into petri dish
and incubate on
histidine-lacking
medium
Ames Test Animation
Rat liver extract
32
Causes of Cancer – Table 20.3 – Common Exposure
33
Causes of Cancer – Table 20.3 – Uncommon Exposure
34
Common Carcinogens in the Home
Consumer products
•
Deodorant, a bar of soap, toothpaste, hair spray,
detergent... All of these products can contain carcinogens
and many do. While each product may only contain a small
amount of cancer-causing agents, most of us use these
products every day.
Making an informed, healthy choice starts by becoming
aware of these products and choosing to use products
made by companies that do not use harmful ingredients.
The list below consists of common consumer products that
contain carcinogenic materials. This is just a start -- please
add to it and share information about other products that
you know of so we can all live more healthy lives.
35
Common Carcinogens in the Home
•
•
•
•
•
•
Bath and beauty products
Dove Beauty Bar: It's 99% water, but watch out for that other 1%. It
includes quaternium 15 and formaldehyde, known carcinogens, as well
as irritants to the skin, eyes, and mucous membranes.
Johnson's Baby Shampoo: Contains carcinogens quaterium 15, FD&C
RED 40, which can cause dermatitis.
Crest Tarter Control Toothpaste: This best selling toothpaste contains
saccharin and phenol fluoride.
Talcum powder: Talc, the main ingredient, is a carcinogen that
increases the risk of ovarian cancer. Use corn starch instead.
Cover Girl Replenishing Natural Finish Make Up (foundation): This
makeup includes BHA, talc, titanium dioxide, triethanolamine. These
interact with nitrites to form nitrosamines and lanolin, which is often
contaminated with DDT and other carcinogenic pesticides.
36
Common Carcinogens in the Home
•
•
•
•
•
•
Household cleaning products
Tide & Cheer Laundry Detergent: Our favorite detergent contains
trisodium nitrilotriacetate, a carcinogen.
Lysol Disinfectant: While it makes the air sweet smelling, it contains the
dioxin.
Food products
Oscar Meyer beef hot dogs: Labeled ingredients in this American
favorite include nitrite, which interacts with meat amines to form
nitrosamines. Tests have also found other carcinogens such as
benzene hexachloride, dacthal, dieldrin, DDT, heptachlor,
hexachlorobenzene, and lindane. If you have to eat hot dogs, look for
ones without nitrates in them.
Whole milk: Certain containers contain DDT, dieldrin, heptachlor,
hexachlorobenzene, recombinant bovine growth hormone and Igf-1. All
of these increase the chances of getting breast, colon and prostate
cancers. Look for RBGH-free organic milk.
•
37
Common Carcinogens in the Home
•
•
Pet products
Zodiac flea collars: These dog collars include the
labeled carcinogen propoxur. Try Trader Joe’s
herbal flea collars instead.
•
•
Other products
Carpets: Some carpets are made or finished with
petrolatum-based chemicals. These chemicals can
"outgas" into the home. Petrolatum is believed to a
human carcinogen.
38
Cancer and the Cell Cycle
•
Oncogenes - genes that when introduced into
normal cells cause them to become cancerous
– Originally discovered by transfection nuclear DNA from tumor cells is isolated and
cleaved into random fragments, and tested
for ability to induce cancer
39
Cancer and the Cell Cycle
40
Cancer and the Cell Cycle
•
Proto-oncogenes are genes encoding proteins
that stimulate cell division.
– Mutated proto-oncogenes become cancercausing genes (oncogenes).
 Mutated alleles of many oncogenes are
genetically dominant.
41
Table 20.4 Some Genes Implicated in Human Cancers
42
Tumor suppressors
•
•
•
•
“Guardian(s) of the genome”
Often involved in maintaining genomic
integrity (DNA repair, chromosome
segregation)
Mutations in tumor suppressor genes lead
to the “mutator phenotype”—mutation
rates increase
Often the 1st mutation in a developing
cancer
43
Tumor-Suppressor Genes
•
Tumor suppressor genes encode proteins
that turn off cell division in healthy cells.
– Cancer may be initiated by the
inappropriate activation of proteins that
regulate the cell cycle, or by the
inactivation of proteins that normally
suppress cell division.
44
p53—a classic tumor suppressor
•
•
•
•
•
“The guardian of the genome”
Senses genomic damage
Halts the cell cycle and initiates DNA repair
If the DNA is irreparable, p53 will initiate the
cell death process
What is the name of the cell death process?
45
Rb—a classic tumor suppressor
•
•
•
Rb binds to a protein called E2F1 and
inhibits its function
E2F1 initiates the G1/S cell cycle transition
Thus, Rb is a crucial cell cycle checkpoint
46
Some Genes Implicated in Human Cancers
Table 20.4
47
Tumor-Suppressor Genes
48
Tumor-Suppressor Genes
49
Cancer and the Cell Cycle
•
Cells control proliferation at several
checkpoints.
– All these controls must be inactivated for
cancer to be initiated.
 Induction of most cancers involves
mutations of several genes.
 explains why most cancers occur in
people over 40
 more time for individual cells to
accumulate multiple mutations
50
The Cell Cycle and Cancer
51
The Stages of the Cell Cycle
1. Click on picture for cell cycle animation –
will go to www.cancerquest.org)
2. Use alt-tab keys to go between website
and power point presentation.
3. Click on blank space to proceed to next slide.)
52
There are several factors that regulate the cell cycle and assure a cell
divides correctly.
1.Before a cell divides,
the DNA is checked to
make sure it has
replicated correctly. (If
DNA does not copy
itself correctly, a gene
mutation occurs.
DNA replication animation:click
on DNA picture
53
2. Chemical Signals tell a cell when to start and stop dividing.
(Target cells animation: click on go
sign)
54
Neighboring cells communicate with dividing cells to
regulate their growth also.
(
Normal contact inhibition animation: click on petri dish)
55
Cancer is a disease of the cell cycle. Some of the body’s cells divide
uncontrollably and tumors form.
Tumor in Colon
Tumors in Liver
56
While normal cells will stop dividing if there is a mutation in the
DNA, cancer cells will continue to divide with mutation.
57
Due to DNA mutations, cancer cells ignore the
chemical signals that start and stop the cell cycle.
2 animations of cancer cells dividing: click on picture
58
Due to DNA mutations, cancer cells cannot communicate with
neighboring cells. Cells continue to grow and form tumors.
Skin cancer
(cancer cells dividing: click on
picture.)
59
SUMMARY
Normal Cell Division
•
•
•
DNA is replicated
properly.
Chemical signals start
and stop the cell
cycle.
Cells communicate
with each other so
they don’t become
overcrowded.
Cancer Cells
1.
2.
3.
Mutations occur in the
DNA when it is
replicated.
Chemical signals that
start and stop the cell
cycle are ignored.
Cells do not
communicate with
each other and
tumors form.
60
Chromosomal Instability
61
Chromosomal Instability as seen in karyotypes
What is the main
difference
between these
images?
62
Smoking and Cancer
•
About one-third of all cancer cases in the
United States are directly attributable to
cigarette smoking.
– Smoke contains many mutagenic
chemicals, and places them in direct
contact with lung tissues.
 damages genes of epithelial cells lining
the lungs
63
Figure 20.16
64
Tobacco Reduces Life Expectancy
65
Potential Cancer Therapy Targets
Preventing the Start of cancer (1-6)
66
Preventing start of cancer
Many therapies work on the cell division
initiation pathway
1. receiving signal to divide
–
–
mutations that increase number of receptors on
cell surface amplify the division signal
Block signals or use immune system to attack
protein signaling molecules
67
Preventing the start of Cancer
2. relay switch
– passage of signal into the cell’s interior
 relay switch stuck in “ON” position
 Block on signals
 Turn off the switch
68
Preventing the start of Cancer
3. amplifying the signal
amplification of signal within cytoplasm
occurs naturally
Disrupt amplification pathway
69
Preventing the start of Cancer
4. releasing the brake used to restrain cell
division
normally Rb blocks E2F
E2F enables cell to copy DNA
when Rb is inhibited DNA copying begins
when Rb is mutated it cannot be inhibited
70
Preventing the start of Cancer
5. checking readiness
ensures DNA is undamaged and ready to
divide
p53 inspects the integrity of DNA
when mutated, DNA checking cannot occur
71
Preventing the start of Cancer
6. stepping on the gas
normally “gas tank is nearly empty”
restore telomerase inhibitors
Cells normally can divide about 30 times,
cancer cells have lost this inhibition
72
Preventing the spread of cancer
7. tumor growth
 angiogenesis inhibitors
 angiostatin & and endostatin
8. metastasis
 cells break off and migrate
73
Benign vs. Malignant Tumors
Benign Tumors
• Benign tumors are not cancerous. They:
• can usually be removed
• do not come back in most cases
• do not spread to other parts of the body and the
cells do not invade other tissues
74
Benign vs. Malignant Tumors
Malignant Tumors
• Malignant tumors are cancerous. They:
• can invade and damage nearby tissues and
organs
• metastasize (cancer cells break away from a
malignant tumor and enter the bloodstream or
lymphatic system to form secondary tumors in
other parts of the body)
75
76