Talk Ten:Stem Cells and Cancer

Chapters 7 & 21

Biology Today (BIOL 109)

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

Figure 12.5aRegulation of gene

expression• Gene transcription begins with the enzyme RNA

polymerase binding to a promoter sequence.

• Allows transcription to occur DNA – RNA - protein

Figure 12.5bRegulation of gene

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

Figure 12.5cRegulation of gene

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

Figure 12.5dRegulation of gene

expression• Repressors are also regulated.

• Transcription is once again allowed

Figure 11.3

Pancreascell

Eye lens cell(in embryo)

Nerve cell

Glycolysisenzymegenes

Crystallingene

Insulingene

Hemoglobingene

Key:

Activegene

Inactivegene

Regulation of gene expression

Gene Structure in Eukaryotes

- contains Exons and Introns - Exons = contains coding info - Introns = does not contain coding info

• introns are interveningsequence that istranscribed but then mustbe removed

• 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 (introns)

• 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

Regulation of gene expression

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

• Normal plant and animal cells have a cell cycle control system

Cancer Cells: Growing Out of Control

• 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 proto-oncogenes 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

• 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

Remember Regulation of gene expression?

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

• Another codes for altered 2nd 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

Figure 12.17 (1)Progression of cancer• Malignant tumors invade normal tissue

• Do not just push healthily cells out of the way

Figure 12.17 (2)Progression of cancer• Tumor cells produce protein-degrading

enzymes that breaks down the connective tissue that holds cells together

Figure 12.17 (3)Progression of cancer• As Malignant tumors invade normal produce

that 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 includes changes in lifestyle

Cancer Prevention and Survival

– 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?