Why Cells Divide

 Development
 Growth
 Tissue Repair
 Immune Expansion
 Cells respond to signals and divide only when it is
necessary
 When growth is finished or a tissue has been
repaired cells stop dividing
The Cell Cycle
 Divide only when they receive positive signals
 proto-ocnogenes
 Stop dividing if there are mutations
 tumor suppressors
 Anchorage dependence
 Contact inhibition
 Need blood supply
 Telomere shortening limits th4e number of cell
divisions
 Tissue repair

Damaged cells and

platelets secrete
GROWTH FACTORS
(positive regulators of cell
division).

GROWTH FACTORS
signals the surrounding
cells to start dividing
Example: Platelets Derived Growth Factor
(PDGF)
 Secreted by platelets
 Promotes cell growth after wounding
 Discovered as necessary for cells to divide in
culture

DAY 1 DAY 2 DAY 3 DAY 4

- PDGF - PDGF - PDGF + PDGF

 Proto-oncogenes
Proto-oncogenes push the cell into entering the cell cycle because they
stimulate the synthesis of proteins involved in cell division
GROWTH
FACTOR
Receptor
TARGET CELL
Hyperactive
Normal product relay protein
of ras gene (product of
ras oncogene)
Every protein marked issues signals
by an arrow is the Relay on its own
proteins
product of a proto-
oncogene
Transcription factor
(activated)

DNA
NUCLEUS Transcription

Protein that Translation

STIMULATES
cell division
1. Repression of genes that are essential for the continuing of the cell
cycle

2. Coupling the cell cycle to DNA damage. As long as there is damaged

DNA in the cell, it should not divide.

3. Some proteins involved in cell adhesion prevent tumor cells from

dispersing, block loss of contact inhibition, and inhibit metastasis.

4. DNA repair proteins are usually classified as tumor suppressors as

well, as mutations in their genes increase the risk of cancer, for
example BRCA
Cell Cycle Check Points
Spindle Assembly
Checkpoint:
G2
Checkpoint: Check Chromosome’s
attachment to spindle
Check for
size,DNA
replication,
G1 Checkpoint:
DNA damage
Check for size,
nutrients, growth
factors, DNA
damage
 When Entering the Cell Cycle Is Not Normal:
Key Concepts in Cancer
 Cancer is caused by rapid and uncontrolled cell
proliferation that forms a tumor. Sometimes
cancerous cells may spread invading other tissues in
the body
 This uncontrolled proliferation occurs when
mutations accumulate in a cell. These mutations
affect the ability of the cell to control its division
cycle.
 Cancer is not one disease, but many different
diseases
 GROWTH
FACTOR
Receptor
TARGET CELL

Hyperactive
Normal product relay protein
of ras gene (product of
ras oncogene)
issues signals
on its own
Relay
proteins

Transcription factor
(activated)

DNA

NUCLEUS Transcription

Protein that Translation

STIMULATES
cell division
When Entering the Cell Cycle Is Not Normal:
Key Concepts in Cancer

 Metastatic cancer also involves mutations other than

those involving cell cycle regulation. Some examples:
• Angiogenesis (growth of blood vessels)
• Loss of contact inhibition
• Loss of anchorage dependence
HeLa immortal cell cells
Genetic Predisposition to Cancer
 Cancer is a “Genetic” disorder, but cancer is NEVER inherited. In most cases is
caused by sporadic mutations in somatic cells.
 Some people inherit alleles that increase their chances of getting specific cancers.
 Breast cancer is one example. The genes that, when mutated predispose women to
breast and ovarian cancer have been discovered. They have been named BRCA1
and BRCA2.
 BRCA1 and BRCA2 are tumor-suppressors. Their normal function is in DNA
repair.
 Mutations in BRCA1 and 2 are loss of function therefore recessive.
 Having the mutation, does NOT mean that an individual is going to get cancer.
Cancer is a multistep process, having a predisposition means that in order to get
cancer you need to accumulate one less mutation. Because the BRCA genes
function in DNA repair, individuals with defective BRCA accumulate mutations
faster.
 When a woman inherits a BRCA mutation, that mutation is present in ALL her
cells. However, the allele does not predispose that woman to leukemia or lung
cancer.
 Control systems in different cell types are different. Consequently the genes
which must be mutated to cause cancer will differ from cell type to cell type.
 Other Risk Factors
 Physical and chemical mutagens. Smoke, high fat
diet, sun exposure increase mutation rates therefore
increase the chance that these mutations will affect
genes involved in the cell cycle
 Age. Every time DNA is replicated there is a chance
that a mutation will occour
 Viruses. Both RNA and DNA. In humans only one
known retrovirus cause cancer, HTLV (human T cell
leukemia virus). Cervical cancer for the most part
caused by human papilloma virus (DNA), EBV can
cause Burkitt’s lymphoma, hepatitis B virus can
cause liver cancer
Why Some Viruses Cause Cancer
 Accidental effect
 Retroviruses insert their genome randomly in the genome of the host.
 Insertion in the coding/regulatory sequence of genes that control cell
division can deregulate the cell cycle
 Retroviruses can “steal” cellular proto-oncogenes and carry them
from cell to cell in a mutated form (Rous Sarcoma)
 As a part of their life cycle
 Some DNA viruses need the cell to enter the cell cycle to replicate
their own DNA, therefore produce proteins that push the host cell
into dividing (Papilloma-HPV)
 Surgery
 Radiation
 Chemotherapy
 Immune Intervention
Allow you to visualize a cell’s “transcriptome” at any particular time or
in a particular condition.

Transcriptome is an indication of which genes are expressed (transcribed)

in a cells at the time when the experiment was done. What you see are
the genes that have been transcribed in a cell at that moment.