Transcript 2-Gene Expression & Development

Gene Expression and
development
Cell differentiation
What controls the
development of
cells and tissues in
multicellular
organisms?
 Regulating gene
expression is
especially important
during
development.
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Cell differentiation
Each of the specialized
cell types found in the
adult originates from a
single fertilized egg
Cells don’t just grow
and divide during
development, they also
undergo diferentiation
to become specialized
for particular functions
Cell differentiation
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As organisms grow
and develop, organs
and tissues develop to
produce a
characteristic form.
The development of
this form is called
morphogenesis.
Homeotic genes
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During development there
are regulatory genes that
determine where certain
structures, such as
appendages, will appear
during morphogenesis. For
example, these genes would
control where legs are
located in a developing fruit
fly.
A mutation in one of these
genes actually results in the
legs of the fruit fly being
placed on the head of the
beast!
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Homeotic genes
These genes are called
homeotic genes. Homeotic
genes determine the body
organization of
multicellular organisms
Within homeotic genes, there
are regions of DNA (130-180
base pairs long) that control
patterns of development
called homeoboxes.
Homeoboxes code for
proteins that enhance
transcription and activate
other genes that are
important in development.
Homeoboxes have a domino
Homeotic genes
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So, back to the original
question,
What casues growth and
development of of cells and
tissues within an organism?
The answer would be that
there are a set of master
control genes (homeotic
genes) that act as switches
that trigger particular
patterns of development and
differentiation in cells and
tissues.
Gene expression and cancer
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So, what if something
goes wrong with cell
differentiation and
growth?
Then you end up with
cancer.
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Gene expression and cancer
A tumor is an abnormal
proliferation of cells
that results from
uncontrolled or abnormal
cell division
The cells of a benign
tumor remain within a
mass. These pose
relatively little threat to
life unless they attain a
size that compresses
vital organs
Most can be removed
via surgery
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Gene expression and cancer
A malignant tumor is
one in which the dividing
cells can invade and
destroy healthy tissues
elsewhere in the body.
Malignant tumors are
what we refer to as
cancer
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The spread of cancer cells
beyond their original site is
called metastasis.
When metastasis occurs,
cells break off from the
original tumor and spread to
new tissues, where they
invade and begin to from
new tumors.
The spread of cancer is
possible because the
growing cells do not
differentiate properly. The
more poorly differentiated
they are, the more they are
able to spread to tissues that
are different than the original
tissue.
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Malignant tumors can be
categorized by the types of
tissues they affect.
Carcinomas grow in the skin
and tissues that line organs of
the body. This includes most of
the common cancer types. For
example, breast, colon, and skin
cancer are all examples of
carcinomas.
Sarcomas are cancers that
grow inside bone and muscle
tissues. These are more rare.
Lymphomas are cancers that
form in the tissues that form
blood cells. Tumors in blood
forming tissues may also cause
leukemia.
Cancer and the Cell cycle
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In normal cells the
frequency of cell division
is governed by several
factors:
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Adequate nutrition
Attached to other cells,
to a membrane or to cell
fibers before it can
divide
Remember, not all cells
are destined to divide.
Can you think of tissue
types in your body in
which the cells never
divide?
Cancer and the Cell cycle
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Normal cells stop dividing after 2050 cell divisions.
Cancer cells will continue to
divide beyond this even when
they are densely packed; they
ignore the normal cellular
message to stop dividing
They also continue to develop
even when they are not
attached to other cells; this is a
trait that facilitates the spread of
cancer to other parts of the body
Causes of Cancer
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What triggers this uncontrolled cell
growth?
In normal cells, growth is controlled by
genes that specifically regulate cell
growth and cell division
These genes code for growth factors;
regulatory proteins that ensure the
events of the cell cycle happen in the
proper sequence and at the appropriate
rate.
Mutations in these genes can lead to
cancer
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Causes of Cancer
Such mutations can occur
spontaneously or can be
the result of exposure to
carcinogens.
Carcinogens are
substances that increase
the risk of cancer.
Examples include:
Tobacco, asbestos, X-rays,
UV light
This would be a good time
for a visit from the rat pack,
don’t you think?
Causes of Cancer
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Most carcinogens
increase the risk of
cancers because they
are actually mutagens.
A mutagen is an agent
that causes mutations in
the DNA of a cell.
Mutagens are responsible for this!
Causes of Cancer
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Whether a person develops
cancer depends on many
factors. Some families have
a higher than average rate of
cancer; leading researchers
to believe that there are
mutations that can be
inherited to cause cancers;
while other cancers are the
result of environmental
exposure to carcinogens.
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So mutations in
gametes are
especially important
since they can be
passed on to
offspring
Causes of Cancer
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Usually, more than one
mutation is necessary to
produce a cancer cell.
This explains why the
risk of cancer goes up
with increased
carcinogen exposure
and with age
The longer an individual
lives, the more mutations
they will accumulate
Causes of Cancer
 The
rate of deaths
caused by cancer
has actually
declined in recent
years. Given that
there is no cure,
can you propose
why this is so?
Oncogenes
 So,
genetically
speaking, what is
really going on with
cancer?
 Cancers are
caused by genes
that code for
uncontrolled cell
proliferation called
oncogenes
Oncogenes
Oncogenes do not
start out as genetic
“bad guys,” initially,
these genes are
normal and control
the rate of cell growth
and differentiation.
 In their normal,
healthy state they are
called protooncogenes.
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Oncogenes
A mutation in a protooncogene may cause
it to produce more
protein or a protein
that is unusually
active in causing cell
division
 The rate of the cell
cycle then increases,
and cancer is the
result
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Oncogenes
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There are genes in the
genome that actually are
designed to suppress
tumor formation
These are called tumorsuppressor genes
These code for proteins
that prevent uncontrolled
cell division.
Mutations in these
genes cause a genetic
predisposition towards
getting cancer
Oncogenes
 BRCA1
&BRCA 2
are examples of
tumor supressor
genes that have
mutated. If you
inherit a faulty copy
of these genes,
your risk of getting
breast cancer
throughout your
lifetime is about
80%
Viruses and cancer
 Many
viruses are
linked to cancer
 This is because of
the way viruses
work.
 They actually
inject their
genetic material
into cells and
insert it into the
cellular genome
Viruses and cancer
So, when the cell
duplicates, it is
copying viral DNA in
addition to its own.
 This viral DNA codes
for genes that make
more viruses.
Eventually, the cell
makes so many
viruses that it bursts,
then the new viruses
are released into your
body to further the
infection.
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Viruses and cancer
 It
is to the
advantage of the
virus to have genes
that stimulate
uncontrolled cell
growth, because
then it has more
“virus factories.”
 So many viral
genes are actually
oncogenes.
Viruses and cancer
 Viruses
can also
cause mutations in
proto-oncogenes
or tumor
supressor genes.
 One example of a
virus we know is
linked to a virus is
cervical cancer is
HPV
Viruses and cancer
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99% of all cervical
cancers are related to
the virus HPV: human
papilloma virus
This virus occurs in over
100 varieties, however
only some of them cause
cancer.
In additon to cervial
cancer, this virus has
been shown to be linked
to cancer of the vulva
and penis as well
cancer of the anus.
Viruses and cancer
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Two variants of the virus
cause genital warts.
These variants do NOT
cause cancer.
Most people never
realized they have
contracted the virus. In
the current generation of
women, it is estimated
that by age 50, between
85-90% of women will
have been exposed to
the virus.
Viruses and cancer
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This is what the new
vaccine Guardasil is
designed to protect
against.
Until recently Guardasil
was only approved for
use in women. Recently,
it has been approved for
use in boys as well.
They key is to administer
these shots prior to the
onset of sexual activity.