Transcript Recombinant DNA Technology

Cancer
A Disease Resulting from
Uncontrolled Cell Growth
Properties of
Cancer Cells
Due to lack of specialization,
cancer cells have a
different appearance
than surrounding cells.
Cancer cells have enlarged nuclei and may have extra chromosomes.
They are genetically unstable and accumulate mutations.
Normal cervical cells
Precancerous
cervical cells
Cancerous
cervical cells
Non-cancerous
cells form sheets.
Properties of
Cancer Cells
Cancer cells grow
into tumors,
showing a lack of
contact inhibition.
Cancer cells do not respond to signals from
Growth factors—stimulate or inhibit cell division
Apoptosis factors—promote death of cells
with damaged DNA
Properties of
Cancer Cells
Cancer cells divide more frequently and for an
unlimited number of times due to an abundance
of telomerase, an enzyme that repairs the ends
of chromosomes
Cancer cells show metastasis, an invasion of
other tissues
Angiogenesis: cancerous tumors grow new blood
vessels for delivery of nutrients and oxygen
Cancer is the result of multiple mutations
causing uncontrolled growth
Angiogenesis: Formation of new
blood vessels, allows tumor to
grow to larger size
Normal Cell Growth Involves
the Cell Cycle with Mitosis
G2
assembly of
components
for division
S
chromosomes
replicate
Mitosis
P M
A
T
Interphase includes
G1 = growth phase 1
S = synthesis phase
G2 = growth phase 2
cytokinesis
G1
cytoplasm
doubles
Interphase
Mitosis includes
P = prophase
M = metaphase
A = anaphase
T = telophase
Chromosomes
align individually
at the cell equator
so each daughter
cell receives one
copy of each
chromosome
Mitosis = Chromosomal Division Leading to Genetically
Identical Nuclei
Control of the Cell Cycle
Mechanisms for controlling progress
through the cell cycle
Extracellular Signals
Control the timing of cell division
Transitions
Orderly progression from one stage of cell
cycle to another
Depend on the production of proteins
called cyclins
Checkpoints
Delay progression to next stage if cell
must repair damage
Control of the Cell Cycle Involves
Activities at Transitions and Checkpoints
Signals initiate
self-destruction if
DNA damage is
severe
Apoptosis
Checkpoint
G2M
Checkpoint
SG2
Transition
G2M
Transition
P M
G2
assembly of
components
for division
S
A
T
Mitosis
cytokinesis
G1
chromosomes
replicate
DNA Damage
Checkpoint
Spindle
Assembly
Checkpoint
cytoplasm
doubles
G1S
Transition
G1S
Checkpoint
Cancer-Causing Mutations Occur in Two Types of Genes
Proto-oncogene
stimulates cell division
mutation
Oncogene
overstimulates cell division
Tumor Suppressor Gene
inhibits cell division
mutation
Mutated Tumor Suppressor Gene
cannot influence cell cycle
Mutations That Cause Cancer
Gene
Type
ProtoOncogene
example
Ras
Tumor
Suppressor
Gene
examples
RB
p53
Normal
Function
In Cancer
In response to
Oncogene
extracellular or Promotes cell
intracellular
division in
signals, promotes
absence of
cell division and
signals
prevents
apoptosis
Inhibits cell
division and
promotes
apoptosis
Active gene
product no
longer
available to
control cell
division
Mutation
Type
Dominant
Recessive
Applying Your Knowledge
TRUE: Thumbs Up
FALSE: Thumbs Down
Indicate whether each statement is TRUE or FALSE
• Cancer cells escape the normal controls on cell
division.
• Oncogenes are recessive mutations.
• The growth of a cancer cell is stopped by
contact with another cell.
• Cancer-causing mutations in tumor suppressor
alleles inhibit cell division.
In cancer cells, the RAS
gene product is locked into
its GTP-binding shape and
does not require a signal at
the receptor in order to
stimulate cell division
Ras Proto-Oncogene
In response to growth factor
binding at receptor, the Ras
gene product combines with
GTP to promote cell division
RB = product of
Retinoblastoma gene,
inhibits action of E2F until
chemically modified due
to buildup of CDK-cyclins
(intracellular signals)
In Normal Cells, the Rb Gene Product
Controls the G1 S Transition
E2F = transcription factor
required to activate genes
for DNA synthesis
In people who are heterozygous for a mutation in the RB gene (Rb+Rb-),
there is a tendency for the functional copy of the RB gene (Rb+) to mutate
to Rb-. Retinal cancer develops because growth of tumor cells is no
longer controlled at the the G1S transition.
p53 = transcription factor that
causes p21 to be produced
In Normal Cells, the p53 Gene Product
Acts at the G1 S Checkpoint Preventing
Entry Into S Phase If DNA Is Damaged
p21 inhibits intracellular signals
that would activate E2F
Cells with
damaged DNA
do not pass the
G1S
checkpoint
In cancer cells the mutated p53 gene
product no longer stimulates p21
production. Cells will pass the G1 S
checkpoint even when chromosomal
damage exists.
In Normal Cells, the p53 Gene Product Stimulates
Apoptosis If DNA Damage Cannot Be Repaired
p53 gives an internal
signal for apoptosis
In cancer cells, a mutated p53
gene product no longer initiates
self-destruction. Cells with
damaged DNA can divide and
more DNA damage can be
accumulated.
p53 is the most frequently mutated
of all known cancer-causing genes,
contributing to many types of cancer.
Applying Your Knowledge
Thumbs Up: Dominant Oncogenic Allele
Thumbs Down: Recessive Tumor Suppressor Allele
Which description best represents the
• Cancer-causing allele for Rb protein?
• Cancer-causing p53 mutation?
• Cancer-causing RAS allele?
Causes of Cancer
• Heredity
– tendency to develop cancer can be
inherited due to mutations in tumor
suppressors, such as BRCA1 and RB
– Tendency to inherit thyroid cancer is
linked to the RET proto-oncogene
• Environmental Carcinogens
– agents that contribute to cancer
development, often by causing
mutations
Causes of Cancer
• Environmental Carcinogens
– Radiation
• ultraviolet radiation in sunlight
• nuclear radiation
• radon gas
– Organic chemicals found in
• tobacco smoke
• pollutants
– Viruses
•
•
•
•
hepatitis B and C viruses
Epstein-Barr virus
human papillomavirus
HIV
Cancer Prevention
• Protective Behaviors
– Avoid Carcinogens
– Get regular screening tests
– Get vaccinated
• Dietary Habits
– Avoid excess weight gain
– Exercise regularly
– Exclude foods that promote cancer–
salt-cured or smoked foods, excess
alcohol
– Limit foods that are high in saturated fat
– Include protective foods with fiber,
vitamins A and C, and cruciferous
vegetables
Treatment of Cancer
• Traditional Therapies
– Surgery
– Radiation
– Chemotherapy
• restore immune function with bone marrow transplants
• Newer Therapies
– Immunotherapy
– p53 gene therapy
• Genetically-engineered adenovirus that can infect and
kill p53-deficient cancer cells
– Antiangiogenic drugs to inhibit blood vessel
formation
– Targeted therapy acting on specific molecules
• Herceptin blocks growth factor receptors on breast
cancer cells
• Gleevec inhibits the action of a faulty tyrosine kinase
related to uncontrolled bone marrow cell reproduction
in Chronic Myelogenous Leukemia