Download Stem Cells and cell division

Stem Cells, cell division,
and Cancer
(Chapter 12)
Compartmentalization
• This permits organisms to become
larger than they would be as single
cells.
• Physical restrictions are imposed
on living things by the ratio of
their surface area to volume ratio.
• Requirements for energy and
wastes increase proportionally to
the volume of an organism
Specialization
• As an organism enlarges, its
volume grows faster than its
surface area.
• The volume of Cube B is 27 times
the volume of cube A
• The surface area of Cube B is only
9 times the surface area of cube A
• It has all to do with nutrient uptake
and the balance with metabolism
Specialization
• An advantage of multicellular organisms is that not every
cell needs to perform every function.
• Allows the formation of specialization – tissues.
• For specialization to be successful, the behavior of one type
of cell must be integrated with the behavior of other cells.
• Cells – tissues – organs – organ systems.
The cell Cycle
• Mitosis is only one step of
a larger process called the
cell cycle.
• The proper functioning of
multicellular organisms depends
on the regulation and
integration of the process in all
cells, particularly in the process
of cell division.
• Normal cells grow only a small
fraction of the time
The cell Cycle
• They continually make new
proteins (ribosomes and rough
endoplasmic reticulum) to
replace those that are damaged
or have been used up
(enzymes).
• Most of the time they do NOT
increase in size.
• When the do grow they reach a
point when the surface to area
ratio makes them insufficient.
• Then they divide
The cell Cycle
• Cell cycle begins with G1, in
which protein synthesis is
increased.
• If cell receives the correct
chemical signal, it enters the S
phase, which DNA replication
occurs.
• When DNA replication is
complete cell enters G2 phase
where it get ready for either
mitosis or meiosis.
The cell Cycle
• Most of the time cells spend
their time in the resting phase
(G0). This is the resting phase.
• Other cellular processes occur
but the cell does not go through
the process to divide unless
signaled to do so.
• The duration of the cell cycle is
constant between species, but
G0 varies greatly
• Depends on nutrients and
chemical signals from
neighboring cells.
Regulation of cell division
• The cell cycle ( and thus cell
division) is tightly regulated in
all types of organisms.
• There must be available space
for the new cell
• Chemical signals must be
properly communicated.
• The dividing cell must be
connected to a surface
Regulation of cell division
• Contact with neighboring cells
suppresses cell division in
normal cells – called contact
inhibition.
• Normal cells receive signals
form the external environment
and do not divide unless they
get a signal to send them from
G0 into the G1 phase – such
molecules are called growth
factors.
• The 1st messenger are
cytokines – bind to specific
receptors
Regulation of cell division
• These cytokines bind to specific
receptors which extend through the
cell membrane.
• Stimulates
2nd
messenger
–
concentration of cyclins in nucleus
change
• When concentration of cyclins is
high cells enter the S phase.
• The response of a cell to divide
depends on
–
–
–
–
–
Signal molecules
Receptors
2nd messengers
Cyclin nuclear proteins
Attachment to external support
Remember the Central Dogma of
Molecular Biology?
• DNA holds the code
• DNA makes RNA
• RNA makes Protein
• DNA to DNA is called
REPLICATION
• DNA to RNA is called
TRANSCRIPTION
• RNA to Protein is called
TRANSLATION
•
Regulation of gene
Figure 12.5a
expression
Gene transcription begins with the enzyme RNA polymerase binding
to a promoter sequence.
• Allows transcription to occur DNA – RNA - protein
•
Regulation of gene
Figure 12.5b
expression
When the polymerases stays attached to the promoter longer more
copies are transcribed
• On the DNA near the promoter there are regulatory gene sequences
called enhancers.
•Enhancers cause polymerase to bind more tightly and more gene
expression occurs
•
Regulation of gene
Figure 12.5c
expression
If repressors bind to the regulatory sequences RNA polymerase is
blocked from the promoter and transcription is halted.
• Thus the cell does not divide
•
Regulation of gene
Figure 12.5d
expression
Repressors are also regulated.
• Transcription is once again allowed
Regulation of gene
expression
Pancreas
cell
Eye lens cell
(in embryo)
Nerve cell
Glycolysis
enzyme
genes
Crystallin
gene
Insulin
gene
Hemoglobin
gene
Key:
Active
gene
Inactive
gene
Figure 11.3
Gene Structure in Eukaryotes
- contains Exons and Introns
- Exons = contains coding info
- Introns = does not contain coding info
• introns are intervening
sequence that is
transcribed but then must
be removed
•
Regulation of gene
expression
Gene expression can be
regulated at 5 later steps too.
• 1 – transcription turned on or
off
• 2- mRNA modified to allow exit
from nucleus
• Removal of non coding regions
(exons)
• If this doesn’t happen gene
expression is halted
•
Regulation of gene
expression
Gene expression can be
regulated at 5 later steps too.
• 3 – Alteration of rate of
translation
• Rapid translation produces more
copies of a protein
• 4 – modification of protein
folding
• The initial amino acid sequence
is often not the final sequence
• Some amino acids are added or
removed.
•
Regulation of gene
expression
Gene expression can be
regulated at 5 later steps too.
• 5 – Effector molecules
• Bind to the final protein
structure
• Change the protein shape to
either speed up or slow down
the activity of the protein
How does this relate
to human
development?
How do we develop?
• On ovulation day, egg and sperm fuse to form zygote.
• Zygote divides, implants onto uterus and grows into Embryo
and hangs out for about 9 months.
• Embryo decides it is time to breathe air, fetal adrenal glands
trigger contractions and out comes baby.
• Baby grows grows grows into child, child undergoes
puberty and becomes adult.
• Adult lives, works, reproduces (perhaps), gets gray hair and
croaks.
REMEMBER!!!!!!!!!
• If viable sperm contact an egg at the time of
ovulation fertilization will occur.
• This “typically” occurs on day 14. Remember Day
1 is first day of menstruation.
• The fertilized egg will implant on day 6.
• The new embryo will begin to produce HCG-Human Chorionic Gonadotripin.
• HCG maintains the corpus luteum and allows the
production of progesterone and estrogen until the
placenta takes over this task.
•
Remember Fertilization
Egg must develop and be released
on ovulation day.
• Egg must be correctly positioned in
the oviduct and attract sperm.
• Vaginal tract must activate sperm.
• Hormonal levels must be exact.
• Ensure only one sperm joins with
egg.
Remember - Fertilization
• Sperm must undergo
capacitation--process of
activation by substances in
female vaginal tract fluids.
• Sperm motor from vagina up
through cervix, uterus, to the
oviduct.
• Many sperm attempt
fertilization, only one
succeeds (except for twins).
Development before
Implantation
• Fertilization
• Cleavage: successive rounds
of cell division. A one cell
zygote--2 cell--4 cell--8 cell-.
• Cleavage occurs in the
oviduct.
• Morula: 16 cell stage--enters
the uterus.
• Key cell differentiation step:
– Trophoblast
– Inner Cell Mass
Development before
Implantation
• Blastocyst
• Hollow ball of cells.
• Each cell is called a blastomere.
• Inner cell mass--become the
embryo.
• Trophoblast--Incredible Altruistic
Cells!
– Escape from the Zona
Pellucida
– Digest through Endometrium
– Initiate HCG secretion
– Form the Placenta
Gastrulation
• Truly the most important day of
your life!
• Process of forming 3 germ layers-this process requires cell
movement.
• Each germ layer forms specific
tissues and organs
– Ectoderm--(blue)--will form
skin and nervous system.
– Mesoderm--(red)--will form
muscles, kidneys, connective
tissue, and reproductive organs.
– Endoderm--(yellow)--will form
digestive tract, lungs, liver and
bladder.
Figure 12.8b
Extraembryonic
Membranes
• Establishing extraembryonic
membranes is critical. These
membranes protect the
embryo and link embryo to
mother:
– Amnion--provides fluid
environment for fetus.
– Chorion--becomes the
placenta--site of gas and
nutrient exchange with mother.
– Allantois--becomes unbilical
blood vessels
The Placenta
• Nutrient and Gas Exchange
between fetus and mother.
• Fetal side--from chorion.
• Maternal side--from uterine
tissue
• Blood of fetus and mother do
not mix.
• Fetal chorionic villi project
into maternal blood.
• Exchange occurs across
membranes.
• Umbilical cord stretches
between placenta and fetus.
Birth Defects
• 1 in 16 newborns (6.25 out of 100) born with birth
defect. Many minor, but some serious or fatal.
• 20% of defects (3.125 out of 1000) are genetic.
• Causes:
– neural tube closure problems--folic acid.
– drugs--aspirin, caffeine, alcohol, vitamin A creams,
cigarette smoke, cocaine, heroine, thalidomide,.
– pathogens--rubella, HIV, STDs, listeria..
Genetic screening
• Amniocentesis--remove
fluid from amniotic
cavity.
• Analyze cells for
genetic abnormalities.
Performed 15th -17th
week of pregnancy
Genetic screening
• Chorionic villi
sampling--remove villi
by suction, test for
genetic abnormalities.
• Performed 5th to 12th
week of pregnancy,
chance of risk for fetus
Genetic screening
• Screening eggs--obtain
eggs and test a polar
body (eggs “clone”).
• If polar body is normal,
fertilize and implant the
egg.
Birth--Hormonal Control
• Fetus--Hypothalamus—Cortisol Releasing
Hormone
• Fetus--Anterior pituitary --ACTH
• Fetus--Adrenal Gland produces Cortisol and
DHEAS.
• Cortisol from fetus converted to prostaglandins in
placenta--these begin contractions.
• DHEAS from fetus converted to estriol in placenta-these promote oxytocin in mother.
• Oxytocin (from Posterior pituitary) in mother
begins labor.
• Cervical stretching--positive feedback.
Birth--Stages
• Stage I:
• water breaks
• cervix dilates
Birth--Stages
• Stage II:
• Contractions increase to
every 1-2 min, baby
emerges.
• Episiotomy (cut vaginal
orifice) can prevent
ripping. Baby emerges,
umbilical cord cut.
Birth--Stages
• Stage III:
• Placenta is delivered
about 15min after birth.
• Remember our
altruistic trophoblast
cells!
Cancer
What Is Cancer?
– Cancer is caused, in part, by a breakdown in control of the
cell cycle
– The cell cycle is controlled by proteins in the cell that give
either a “GO”, a “STOP” or a “die” signal
– Cancer cells divide excessively
- they have too many “GO” signals or
not enough “STOP” signals
- cancer cells can also ignore “die” signals = apoptosis
Cancer Cells: Growing Out of
Control
• Normal plant and animal cells have a cell cycle
control system
• When the cell cycle control system malfunctions
– Cells may reproduce at the wrong time or place
– A benign tumor may form
Cancer Cells: Growing Out of
Control
• Proto-oncogenes –
• Genes whose products signal
and regulate normal cell
division
• The abnornal, mutated form
of the proto-oncogene that
lead to cell transformation
and cancer are called
oncogenes.
Cancer Cells: Growing Out of
Control
• Oncogenes differ from protooncogenes in three basic ways
• 1- Timing and quality of
expression
• 2- Structure of protein products
• 3 – Degree to which their protein
products are regulated by cellular
signals
Remember Regulation of gene
expression?
• Gene expression can be
regulated at 5 later steps too.
• 1 – transcription turned on or
off
• 2- mRNA modified to allow exit
from nucleus
• 3 – Alteration of rate of
translation
• 4 – modification of protein
folding
• 5 – Effector molecules
Cancer Cells: Growing Out of
Control
• The mutation of a proto-oncogene
to an oncogene can alter the cell
division signals at any of the 5
steps and trigger uncontrolled cell
division
• One type of oncogene codes for a
modified growth factor that
continuously 2nd messengers and
thus always triggers cell division
• Another causes the cell to secrete
growth factors allowing the cell to
divide
Cancer Cells: Growing Out of
Control
nd
• Another codes for altered 2
messenger that tells the cell to
activate cell division
• Another alters the regulatory
system in the nucleus
– So the DNA continues to
replicate and this drives
continuous cell division
Six Hallmarks of Cancer
1. Self-sufficiency in growth signals or response
2. Insensitivity to grown inhibitor signals (antigrowth signals)
3. Evasion of programmed cell death (apoptosis)
4. Limitless replicative potential (no senescence)
5. Sustained angiogenesis (stimulation of blood vessel growth)
6. Tissue invasion and metastasis
Progression of cancer
• There are several mechanisms which prevent mutations causing
cancer
• A mismatch leads to a permanent mutation on one DNA strand if not
corrected
Progression of cancer
• A mismatch repair protein (spell-checking protein) acts on a mutated
DNA strand
• Cuts out the DNA and allows the correct base to be added
What cancer affects - Tissues
• Tissue: Similarly specialized cells that perform
a common function in the body.
• 4 main tissue types in the human body:
– 1. Epithelial: covers body surface and lines body
cavities.
– 2. Connective: binds and supports body parts.
– 3. Muscular: Moves body parts
– 4. Nervous-Receives, interprets and sends signals.
Tissues require cell
junctions
• What holds cells
together?
• Cell Junctions, three
main types:
– 1. Tight Junction: seams
– 2. Gap Junctions:
communication
– 3. Adhesion Junctions:
sticky rivits
Connective Tissue
•
•
•
•
•
•
Binds Organs together
Holds epithelium to the body
Provides Protection and Support
Produces Blood Cells
Stores Fat
CT cells secrete a matrix, this matrix is composed
of fluid and fibers-collagen and elastin.
Progression of cancer
• A tumor is said to be benign if it is contained in one
location and has not broken through the basement
membrane to which normal cells are attached
• Benign tumors often cause no health problems to an
individual
• Can grow big enough to interrupt the functioning of normal
tissue
• Removal is generally successful as they are not intermingled
with other tissue
•
Progression
of
cancer
Figure
12.17
(1)
Malignant tumors invade normal tissue
• Do not just push healthily cells out of the way
•
Progression
of
cancer
Figure
12.17
(2)
Tumor cells produce protein-degrading enzymes that breaks
down the connective tissue that holds cells together
Progression
of
cancer
Figure
12.17
(3)
Malignant tumors invade normal produce that
• As
allow
them to invade other tissue, they spread to other locations
• Metastasis – one or more transformed cells spread to the
rest of the body via the blood system.
Figure 12.19a
Figure 12.19b
Cancer Prevention and Survival
• Cancer prevention includes changes in
lifestyle
– Not smoking
– Avoiding exposure to the sun
– Eating a high-fiber, low-fat diet
– Visiting the doctor regularly
– Performing regular self-examinations
- Chemoprevention
Issues
• So, what do you thing of stems cells now if they can be used
to:
– Hopefully grow new organs
– Treat all forms of cancer
– Possibly treat all major diseases
– Stop a lot of pain and suffering
The end!
Any questions?