Transcript Cancer cells

Cell Reproduction
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Understand why cells reproduce
Describe the structure of the chromosome
Describe the cell cycle
Describe each phase of mitosis
Distinguish between mitosis and meiosis
Describe the process and phases of meiosis
Terms
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Anaphase
Asexual reproduction
Autosomes
Cell cycle
Cell plate
Centromere
Centrioles
Centrosome
Cleavage furrow
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Chromosome
Crossing over
Cytokinesis
Diploid
Gamete
G1
G2
Haploid
Histone
Interphase
Meiosis
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Metaphase
Mitosis
Microtubules
Prophase
Restriction point
S phase
Sexual reproduction
Sex chromosome
Spindle
Somatic cell
Synapsis
Telophase
Tetrad
Why Cells Must Reproduce
• Cells are limited in size due to:
– Surface area to volume ratio: S.A./volume
• Volume increases 8x faster than surface area
• The area in the ‘middle’ of the cell cannot get
nutrients in or wastes out because there is not
enough surface area for diffusion
– Amount of DNA – limited amount of instructions,
cell cannot keep up with demand
Why Cells Must Reproduce
• To grow an organism must produce more cells
• Each new cell must have an
accurate copy of the DNA
(genome)
• Mitosis
– Growth
– Replace cells that wear out
– Replace damaged cells
– Asexual reproduction
Purposes of Mitosis
• Asexual reproduction:
– Unicellular organisms
• Amoeba, paramecium
– Multicellular organisms
• Corals, sponges, plants
Genome
• Genome – cell’s genetic information
– Prokaryote = single, long DNA
molecule (?)
• E. coli – 1700 genes
• Binary fission – bacteria cell division
– Eukaryote = lots of DNA
• Humans – 3.2 b nucleotides
– 25,000 genes (est. HGP ’09)
– Coils up to form 46 chromosomes
Chromosomes
• Genome – genes
• Genes - sections of DNA that are the code for
making the cell’s proteins
• Chromatin – DNA + histones (proteins) ‘at work’
– Making proteins
Chromatin
Chromosomes
• Chromatin coils up to become
chromosomes
– Chromosomes are
‘gene packages’
Chromosomes
• Each chromosome = two
sister chromatids (identical
DNA)
• Centromere = connects the
two chromatids
Chromosomes
• Each species has a characteristic number of
chromosomes
– Human somatic cells (body cells) have 46
(diploid number)
– Dogs = 78, goldfish = 96
– Human gametes (sperm or eggs) have 23
(haploid)
Karyotype
• Karyotype – arrangement of chromosomes
– Picture taken during metaphase
– Size
– Centromere location
– Staining pattern
Normal male
Cell Cycle
• Life history of
the cell
• Interphase
• Mitosis
Cell Cycle - Interphase
• Cell growth
• 90% of cell cycle
– Three subphases:
• G1 (“first gap”) growth
• S (“synthesis”) DNA is
copied
• G2 (“second gap”) cell
completes preparations for division
Cell Cycle - Interphase
• Some cells may enter G0
– Don’t return to
mitosis
– Liver, nerve, muscle
Cell Cycle – M-phase
• Mitosis – division of the nucleus and
chromosomes
• Cytokinesis – division of the cytoplasm and
organelles
Cell Cycle – M-phase
• Mitosis is a continuum:
– For description, mitosis is usually broken
into five subphases:
• Prophase
• Prometaphase
• Metaphase
• Anaphase
• Telophase
Cell Cycle - Interphase
• Late interphase (G2)
• DNA has been copied
– ‘S’ phase
– Chromatin – not chromosomes yet
• Centrosomes have been duplicated
– Microtubules (cytoskeleton)
– Will help form the spindle
Cell Cycle – M-phase
• Prophase - the chromosomes are
coiled, with sister chromatids
• The nucleoli disappear
• The mitotic spindle begins to form
• Centrosomes move toward opposite
poles
• Spindle fibers (microtubules) begin
to grow between the centrosomes
Cell Cycle – M-phase
• Late Prophase - nuclear envelope
disintegrates so that spindle fibers can
attach to the chromosomes
• Kinetochores – special regions of the
spindle, from each pole attach to the
centromere
Cell Cycle – M-phase
• Metaphase - spindle fibers push the sister
chromatids until they are all arranged at the
metaphase plate
• Shortest phase of cycle
Cell Cycle – M-phase
• Anaphase - centromeres divide,
separating sister chromatids
• Each chromatid is pulled toward
the pole to which it is attached
by spindle fibers
Cell Cycle – M-phase
• Telophase - cell continues to
elongate
– Two nuclear envelopes
begin to reform
– Chromosome uncoils
– Nucleolus reforms
• Cytokinesis begins
Fig. 12.9
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
Cytokinesis Divides Cytoplasm
• Animal cells:
• Cleavage furrow –
microfilaments of actin and
myosin form and contract like a
drawstring
• Contraction of the ring pinches
the cell in two
Cytokinesis Divides Cytoplasm
• Plants have cell walls
• Cell plate - vesicles from the
Golgi coalesce at the
metaphase plate
– Plate enlarges until fused
with the plasma membrane
Cell Cycle Control
• Checkpoints in the cycle are controls
– Chemical signals
– Checks to be sure all steps are completed
– Cells also receive signals from outside
(ex. Growth hormones)
• 3 checkpoints; G1, G2, and
M phases
• G1 - Restriction point
Cell Cycle Control
• Frequency of cell division varies with cell type
– Skin cells divide frequently; exercise
– Liver cells do not divide unless damaged
– Nerve and muscle cells do not appear to divide
after maturity
• Much is not yet understood
– How and why are cells preprogrammed to become
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– How and why do some cells become cancerous?
Cell Cycle Control
• G1 checkpoint (restriction point) is most
important.
– Go signal = completes cell cycle and
divides.
– No go = cell exits cycle; switches to nondividing state, G0 phase
Cell Cycle Control
• Density-dependent inhibition
– Cultured cells normally
divide until they form a
single layer
– Cells will grow to fill a gap
– At high densities, not
enough growth factor
and nutrient for all cells
Cell Cycle Control
• Anchorage dependence - cells must be
anchored to a substrate (extracellular matrix)
• Cancer cells do not respond to density-dependent
inhibition or anchorage dependence
Cancer Cells Not Under Cell Cycle
Controls
• Cancer cells do not stop dividing when growth
factors are depleted
– Manufacture their own growth factors (?)
– Abnormality in the signaling pathway
– Problem in the cell cycle control system
• If cancer cells stop dividing, they do so at
random, not the normal checkpoints
Cancer
• Cancer cells may divide indefinitely if they
have a continual supply of nutrients
• Normal cells divide 20 to 50 times (in vitro)
before they stop, age, and die.
– Cancer cells may be “immortal”
• Cells (HeLa) from a tumor removed from a
woman (Henrietta Lacks) in 1951 are still
reproducing in culture.
Cancer
• A cell in a tissue undergoes a transformation
converts it from normal to cancer
– Normally, immune system recognizes and
destroys transformed cells
– Some cells escape destruction and reproduce
to form a tumor, a mass of abnormal cells
Cancer Tumors
• Two types: benign, malignant
• Benign – tumor remains at original site –
surgery
• Malignant – cell leave original site, spread
to other organs
• Metastasis – tumor cells pop ‘loose’ enter
lymph
Cancer - Treatment
• Surgery
• Radiation and chemotherapy
• Interrupt cell cycle
– Mitotic spindle
– Block chemical controls
The next few slides are
of various skin cancers,
the most common type
of cancer. You do not
have to look……
Squamal cell carcinoma
WARNING: the
following picture may
cause you to lose your
lunch….
Normal border
Irregular border
Malignant melanomas
Actinic Keratosis:
‘Pre-cancer’
‘Tags’: benign tumor
Seborrheic Keratosis:
benign melanocyte
‘tumor’
Meiosis
Cell Reproduction
That Produces Gametes
Meiosis
• Gametes (eggs or sperm) are produced only in
gonads (ovaries or testes)
• Cells undergo meiosis in the
gonads
– Produces four daughter cells;
half the chromosomes of
each parent (haploid)
• Fertilization - gametes fuse
together; restores the number to 46. (diploid)
Meiosis
• Chromosomes are homologous pairs
– 23 pairs of homologous chromosomes
• 22 pairs of autosomes
1 pair of sex chromosomes
– Same genes
– Requires two parts for
every gene – one
homologue from one
parent and the other from the other parent
Meiosis
• During ‘S’ each homologue is copied
Meiosis
• Meiosis takes place in two steps
– Meiosis I
– Meiosis II
• Phases are the same but happen twice
– Prophase
– Metaphase
– Anaphase
Interphase
– Telophase
Meiosis
• Prophase I
– Same as prophase of mitosis – except:
• Synapsis - homologous chromosomes
pair up side-by-side
• Crossing over - tips of chromosomes may
swap places
• Value of crossing over?
Prophase I
Crossing over
Meiosis
• Metaphase I
– Chromosome pairs line up at the middle
Metaphase I
Meiosis
• Anaphase I
– Chromosome pairs separate and migrate
to opposite poles
– In mitosis, chromatids separate and
migrate to poles
Anaphase I
Meiosis
• Telophase I
– Chromosome pairs arrive at the pole
– Chromosomes uncoil
– Nuclear envelope forms
– Cytokinesis
Telophase I
Meiosis
• Meiosis II
– Prophase II
– Metaphase II
Meiosis II
– Anaphase II
– Telophase II
– 4 new haploid cells called gametes are
produced
Meiosis
• Produces:
– 4 non-identical, haploid gametes
– Haploid gametes unite to form a zygote
• Zygote undergoes mitosis to become a baby
– Random chance determines which
chromosome you inherit from each parent
– Crossing over increases genetic variation
Goofs in the Process
• Nondisjunction
– Chromatids fail to separate during
meiosis
– One gamete gets and extra chromosome
– The other gamete is missing the
chromosome
Chromosome Alterations: Human
Disease
• Down’s syndrome = trisomy of No. 21;
extra muscular tissue, tongue, eye pads
(diamond-shaped eyes), mental retardation,
heart defects
• Linked to age
• First meiotic division as a fetus, meiosis II
during ovulation
Chromosome Alterations: Human
Disease Sex Genes
• Males:
• Klinefelter’s = XXY; small testis, breasts,
sterile, feminine contours
• XYY = normal, taller than average
Chromosome Alterations: Human
Disease Sex Genes
• Females:
• Metafemales = XXX; limited fertility,
retardation
• Turner’s = XO; sterile, short, no secondary
sex characteristics, no mature ovaries
Comparison of Mitosis and Meiosis
• Mitosis
– 2 identical cells
– New cells are diploid
– Growth, repair,
asexual reproduction
– No synapsis or
crossing over
– One cell division
• Meiosis
– 4, non-identical cells
– New cells are haploid
– Sexual reproduction
– Synapsis and crossing
over
– Two cell divisions
Mitosis and Meiosis
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How are mitosis and meiosis alike?
DNA is replicated
Phases are the same
Spindle forms
Cytokinesis
Cells are reproduced