Transcript Chap 8 – Cancer and Regulation of Cell Cycle

Chapter 8
The Cellular Basis of Reproduction
and Inheritance
PowerPoint Lectures for
Campbell Biology: Concepts & Connections, Seventh Edition
Reece, Taylor, Simon, and Dickey
© 2012 Pearson Education, Inc.
Lecture by Edward J. Zalisko
REGULATION OF THE CELL
CYCLE AND CANCER
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Cancer and Regulation of the Cell Cycle
 Cancer is the result of unregulated cell division!
 Development of cancer is a multi-step process
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Normal Cell Division is a Regulated Process
 Cell division is controlled by
– the presence of essential nutrients,
– growth factors, proteins that stimulate division
– Ex: VEGF, PDGF
– Check-points along cell cycle
– Signals that limit cell division
– density-dependent inhibition, in which crowded
cells stop dividing, and
– anchorage dependence, the need for cells to be in
contact with a solid surface to divide.
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Figure 8.7A
Cultured cells
suspended in liquid
The addition of
growth
factor
Figure 8.7B
Anchorage
Single layer
of cells
Removal
of cells
Restoration
of single
layer by cell
division
Characteristics of Cancerous Cells
 Divide when they aren’t supposed to
 lose dependence on growth factors signals
 ignore STOP signals and cell cycle checkpoints
 Lose density-dependent inhibition
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Checkpoints in the Cell Cycle: Quality Control Systems
GO = cell not actively
involved in division
process
If a cell fails any checkpoint - default is arrest of cell
cycle and/or cell death
Figure 8.8B
Growth
factor
EXTRACELLULAR FLUID
Plasma membrane
Relay proteins
Receptor
protein
Signal
transduction
pathway
G1
checkpoint
G1
S
Control
system
M
G2
CYTOPLASM
THE GENETIC BASIS
OF CANCER
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Cancer and Regulation of the Cell Cycle
 Cancer is the result of unregulated cell division!
 Development of cancer is a multi-step process
 Requires the accumulation of multiple DNA mutations in
genes that regulate normal cell pathways
1
Chromosomes mutation
Normal
cell
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2
mutations
3
4
mutations mutations
Malignant
cell
What is a mutation?
 Change in DNA sequence of a cell
 Germline mutation
– A change in the DNA sequence that can be inherited
from either parent
 Somatic mutation
– A change in the DNA sequence in cells other than sperm
or egg
– The mutation is present in the cancer cell and its
offspring, but not in the patient’s healthy cells
Examples of mutations
Sequence 1
ACTCGTTAGGCA
ACTCGTTAGGCA
Sequence 2
ACTCCTTAGGCA
ACTCGGCA
Type
Substitution
Deletion
ACTCGTTAGGCA
ACTCGTTATCAGGCA
Insertion
ACTCGTTAGGCA
ACTTTGCAGGCA
Inversion
ACTCGTTAGGCA
ACTCGTTAGTTAGGCA
Duplication
11.16 Cancer results from mutations in genes
that control cell division
 Mutations in two types of genes can cause cancer.
1. Oncogenes
– Proto-oncogenes are normal genes that promote cell division.
– Mutations to proto-oncogenes create cancer-causing
oncogenes that often stimulate cell division.
– Ras
2. Tumor-suppressor genes
– Tumor-suppressor genes normally inhibit cell division or
function in the repair of DNA damage.
– Mutations inactivate the genes and allow uncontrolled division
to occur.
– p53
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Ras - A proto-oncogene

Proto-oncogenes STIMULATE cell division
– In a healthy cell, ras relays a signal to cell when growth factor
binds to a receptor, initiating cell division
– Mutations in ras occur in more than 30% of human cancers.
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Figure 11.18A
Growth factor
Receptor
Target cell
Hyperactive
relay protein
(product of
ras oncogene)
issues signals
on its own
Normal product
of ras gene
Relay
proteins
Transcription
factor
(activated)
CYTOPLASM
DNA
NUCLEUS
Transcription
Protein that
stimulates
cell division
Translation
p53 - A Tumor Suppressor Gene

p53 is a protein that normally inhibits cell division.
– In the absence of functional p53, cell division continues because
the inhibitory protein is not produced.
– Mutations in p53 occur in more than 50% of human cancers.
Tumor-suppressor gene
Mutated tumor-suppressor gene
Normal
growthinhibiting
protein
Cell division
under control
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Defective,
nonfunctioning
protein
Cell division
not under control
Figure 11.18B
Growth-inhibiting
factor
Receptor
Relay
proteins
Transcription factor
(activated)
Nonfunctional transcription
factor (product of faulty p53
tumor-suppressor gene)
cannot trigger
transcription
Normal product
of p53 gene
Transcription
Protein that
inhibits
cell division
Translation
Protein absent
(cell division
not inhibited)
DNA Mutations
 What is a mutation?
 Any change in DNA sequence
 May alter function of protein it codes for
 Where do mutations come from?
 You inherit them from your parents
 Inheriting a mutation in a gene that regulates cell cycle leaves
you more susceptible to cancer
 Errors in DNA replication
 Environment
 Carcinogens = chemicals that can alter DNA sequence
 UV light
 X-rays and ionizing radiation
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Importance of somatic DNA changes in human cancer
Both
Inherited
Somatic
Only 5 –10% of cancer cases have a clear hereditary component,
e.g. BRCA1 and BRCA2 in breast cancer
Even in those cases where susceptibility is clearly inherited, somatic
changes are required for cancer to develop