1.

Cancer and the cell cycle

checkpoints, reqmts to advance
oncogenes
tumor suppressor genes

2. 6 Traits of cancerous cells

3. Origins of cancerous cells

 DNA
Mitotic Phase (M)
DNA

DNA DNA
Interphase
DNA
DNA

Cytokine
Mi
to
si

sis
s
G1
G2 Cell growth
Cell growth
preparation for
division
Interphase

S
DNA replication

DNA
DNA
DNA

Interphase
• Proteins within the cell control the cell cycle
– Signals affecting critical checkpoints determine
whether the cell will divide (cyclins, kinases)

G1 checkpoint

Control
system

M checkpoint Figure 8.9A

G2 checkpoint
 Anchorage, cell density, and chemical growth factors
affect cell division

• In laboratory cultures, normal cells divide only

when attached to a surface
= anchorage dependent
• Cells continue dividing until they touch one
another
= density-dependent inhibition

Cells anchor to dish surface and

divide.

When cells have formed a

complete single layer, they stop
dividing (density-dependent
inhibition).

If some cells are scraped away,

the remaining cells divide to fill
the dish with a single layer and
then stop (density-dependent
inhibition).
Figure 8.8A
• Growth factors are proteins secreted by cells
that stimulate other cells to divide

After forming a single layer, cells

have stopped dividing.

Providing an additional supply of

growth factors stimulates further
cell division.

Figure 8.8B
• Growth factors bind to specific receptors on the
plasma membrane to trigger cell division

Growth factor

Plasma membrane

Relay
Receptor proteins G1 checkpoint
protein
Signal
transduction Cell cycle
pathway control
system

Figure 8.8B
• Cancer cells have abnormal cell cycles
– divide excessively and form tumors
 Cancer
• Cancer is one of the most common diseases in the
developed world:
• 1 in 4 deaths are due to cancer
• 1 in 17 deaths are due to lung cancer
• Lung cancer is the most common cancer in men
• Breast cancer is the most common cancer in women
• There are over 100 different forms of cancer
 Cancer
• The division of normal cells is precisely controlled.
New cells are only formed for growth or to replace
dead ones.
• Cancerous cells divide repeatedly out of control even
though they are not needed, they crowd out other
normal cells and function abnormally. They can also
destroy the correct functioning of major organs.
 What causes cancer?
• Cancer arises from the mutation of a normal
gene.
• Mutated genes that cause cancer are called
oncogenes.
• It is thought that several mutations need to occur
to give rise to cancer
• Cells that are old or not functioning properly
normally self destruct and are replaced by new
cells.
• However, cancerous cells do not self destruct and
continue to divide rapidly producing millions of
new cancerous cells.
• A factor which brings about a mutation is
called a mutagen.

• A mutagen is mutagenic.

• Any agent that causes cancer is called a

carcinogen and is described as carcinogenic.

• So some mutagens are carcinogenic.

• Ionising radiation – X Rays, UV light

• Chemicals – tar from cigarettes

• Virus infection – papilloma virus can be responsible

for cervical cancer.

• Hereditary predisposition – Some families are more

susceptible to getting certain cancers. Remember you
can’t inherit cancer its just that you maybe more
susceptible to getting it.
 Benign or malignant?
• Benign tumours do not spread from their site of origin, but
can crowd out (squash) surrounding cells eg brain tumour,
warts.

• Malignant tumours can spread from the original site and

cause secondary tumours. This is called metastasis. They
interfere with neighbouring cells and can block blood
vessels, the gut, glands, lungs etc.

• Why are secondary tumours so bad?

• Both types of tumour can tire the body out as they both
need a huge amount of nutrients to sustain the rapid
growth and division of the cells.
 The Development of Cancer
• Within every nucleus of every one of the
human body's 30 trillion cells exists DNA, the
substance that contains the information
needed to make and control every cell within
the body. Here is a close-up view of a tiny
fragment of DNA.
 1. DNA of a normal cell

• This piece of DNA is an exact copy of the DNA from which it

came. When the parent cell divided to create two cells, the
cell's DNA also divided, creating two identical copies of the
original DNA.
 2. Mutation of DNA

• Here is the same section of DNA but from another cell. If you can
imagine that DNA is a twisted ladder, then each rung of the ladder is
a pair of joined molecules, or a base pair. With this section of DNA,
one of the base pairs is different from the original.

This DNA has suffered a mutation, either through mis-copying (when

its parent cell divided), or through the damaging effects of exposure
to radiation or a chemical carcinogen.
 3. Genetically altered cell

• Body cells replicate through mitosis, they respond to their

surrounding cells and replicate only to replace other cells.
Sometimes a genetic mutation will cause a cell and its
descendants to reproduce even though replacement cells
are not needed.
The DNA of the cell highlighted above has a mutation that
causes the cell to replicate even though this tissue doesn't
need replacement cells at this time or at this place.
 4. Spread and second mutation

• The genetically altered cells have, over time, reproduced unchecked,

crowding out the surrounding normal cells. The growth may contain
one million cells and be the size of a pinhead. At this point the cells
continue to look the same as the surrounding healthy cells.
After about a million divisions, there's a good chance that one of the
new cells will have mutated further. This cell, now carrying two
mutant genes, could have an altered appearance and be even more
prone to reproduce unchecked.
 5. Third mutation

• Not all mutations that lead to cancerous cells result in the cells
reproducing at a faster, more uncontrolled rate. For example, a
mutation may simply cause a cell to keep from self-destructing. All
normal cells have surveillance mechanisms that look for damage or
for problems with their own control systems. If such problems are
found, the cell destroys itself.
Over time and after many cell divisions, a third mutation may arise. If
the mutation gives the cell some further advantage, that cell will
grow more vigorously than its predecessors and thus speed up the
growth of the tumour.
 6. Fourth mutation

• The new type of cells grow rapidly, allowing for more

opportunities for mutations. The next mutation
paves the way for the development of an even more
aggressive cancer.

At this point the tumour is still contained.

 7. Breaking through the membrane

• The newer, wilder cells created by another mutation are able

to push their way through the epithelial tissue's basement
membrane, which is a meshwork of protein that normally
creates a barrier. The invasive cells in this tumour are no
longer contained.

At this point the cancer is still too small to be detected.

 8. Angiogenesis

• Often during the development of earlier stages of the tumour, or

perhaps by the time the tumour has broken through the basement
membrane (as pictured above), angiogenesis takes place.
Angiogenesis is the recruitment of blood vessels from the network
of neighbouring vessels.
• Without blood and the nutrients it carries, a tumour would be
unable to continue growing. With the new blood supply, however,
the growth of the tumour accelerates; it soon contains thousand
million cells and, now the size of a small grape, is large enough to be
detected as a lump
 9.Invasion and dispersal

• The tumour has now invaded the tissue beyond the basement
membrane.

Individual cells from the tumour enter into the network of

newly formed blood vessels, using these vessels as highways
by which they can move to other parts of the body. A tumour
as small as a gram can send out a million tumour cells into
blood vessels a day.
 • What makes most
10. Tumour cells tumours so lethal is their
ability to metastasize --
travel - metastasis that is, establish new
tumour sites at other
locations throughout the
body.
Secondary tumours.

• Metastasis is now
underway, as tumour
cells from the original
cancer growth travel
throughout the body.
Most of these cells will
die soon after entering
the blood or lymph
circulation.