Chapter 1

BIOL2120 CELL BIOLOGY 24

9. Cancer –
Cancer Cells
A First
Look
Benign and malignant tumors

• As the abnormal dividing cells accumulate, the

normal organization and function of the tissue is
disrupted
o Benign tumors grow in a confined local area
and are rarely dangerous
o Malignant tumors can invade surrounding
tissues, and spread throughout the body

• Cancer refers to any malignant tumor and is an

example of a disease that arises from
abnormalities in cell function

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Types of cancers

• Carcinomas, e.g., lung, breast, and colon

cancer, arise from epithelial cells that cover
external and internal body surfaces

• Sarcomas develop from supporting tissues,

e.g., bone, cartilage, fat, and muscle

• Lymphomas and leukemias arise from cells of

lymphatic and blood origin, respectively

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Cancer Cell Proliferation Is
Anchorage-Independent and
Insensitive to Population Density

• Normal cells will only grow well in

culture with solid surface to attach to

• Cancer cells circumvent this process

grow in culture with or without a solid
support (anchorage-independent
growth)

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• Normal cells grown in
culture divide until the
surface of the vessel
is covered by a
single layer of cells
(density-dependent Normal cells
inhibition of growth)

• Cancer cells show

reduced sensitivity to
density-dependent
growth
Cancer cells 5
Defects in Signaling Pathways, Cell
Cycle Controls, and Apoptosis
Contribute to Uncontrolled
Proliferation
• Proliferation is regulated by growth factors that
bind cell surface receptors and activate signaling
pathways in the target cells

• Normal cells do not divide unless stimulated by

the proper signals

• Cancer cells alter signaling pathways to create a

constant signal to divide
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Disruptions in cell cycle control

• The commitment to proceed through the cell cycle is

made at the restriction point (G1 to S progression)

• Under suboptimal conditions, normal cells arrest at

the restriction point and cease dividing

• Under comparable conditions, cancer cells continue

to divide due to defects in cell cycle controls

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Apoptosis
• Cell death is controlled mainly by pathways that
trigger apoptosis to remove unnecessary or
defective cells

• Cancer cells are defective and unnecessary but

elude apoptosis by blocking the pathway

• In some cancers uncontrolled growth arises

more from failure to undergo apoptosis than
from increased cell division

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Oncogenes and Tumor Suppressor
Genes

• Gene mutations and changes in gene

expression play a central role in development
of cancer

• The mutations mostly affect genes that control

cell proliferation and survival

• There are two main classes: oncogenes and

tumor suppressor genes

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Oncogenes Are Genes Whose
Products Can Trigger the Development
of Cancer

• An oncogene is a gene whose presence can

trigger cancer
o Mutation of normal genes
o Cancer-causing viruses

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Proto-oncogenes Are Converted into
Oncogenes by Several Distinct
Mechanisms

• Oncogenes arise by mutation from normal cellular

genes called proto-oncogenes (normal cellular
genes that contribute to the regulation of cell
growth and survival)

• When their structure or activity is disrupted by

mutation through several mechanisms, the mutant
form of the gene can cause cancer

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Chromosomal Translocation

• A part of one chromosome is joined to another

chromosome

• In Burkitt lymphoma (a cancer of B

lymphocytes), the translocation moves the MYC
gene (encoding a transcription factor that
stimulates cell proliferation) from chromosome 8
to a highly active region of chromosome 14
(encoding for antibody molecules)

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13
Most Oncogenes Code for
Components of Growth-Signaling
Pathways

• Several hundreds of oncogenes have

been identified

• Many of them encode proteins in one of

the six categories related to steps in
growth-signaling pathways

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 1. Growth factors

3. Plasma membrane
2. Receptors GTP-Binding
proteins

4. Protein Kinases

6. Cell cycle and 5. Transcription factors

apoptosis
regulations
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16
Tumor Suppressor Genes Are Genes
Whose Loss or Inactivation Leads to
Cancer

• The loss or inactivation of tumor

suppressor genes can also lead to cancer

• The normal function of such genes is to

restrict cell proliferation

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 http://www.doctortipster.com/wp-content/uploads/2011/11/Retinoblastoma.jpg

• Hereditary retinoblastoma, a rare eye cancer

develops in young children with a family history of the
disease
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Identification of the RB gene

• The pattern of development

of the disease suggests that
o Chromosome 13
contains a gene that
normally inhibits
proliferation
o Deletion or disruption of
both copies must occur
before cancer develops

• The RB gene was identified

as the missing gene

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Role of Rb
• The product of the RB gene, Rb protein controls the G1 to S
phase progression in the cell cycle

• Disrupting both copies of RB opens the door to uncontrolled

proliferation

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The p53 Tumor Suppressor Gene Is the
Most Frequently Mutated Gene in Human
Cancers

• One of the most important tumor

suppressor genes identified is the
p53 gene
o ~ 50% of all cancers have p53
mutations

• p53 responds to DNA damage by

arresting the cell cycle to allow DNA
repair, and triggering apoptosis if
repairs cannot be made

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p53 in cancer

• Inactivation of p53 leads to a failure of

apoptosis, and allows defective cells to
continue to divide

• An inherited condition, Li-Fraumeni syndrome,

is caused by a defective copy of the p53 gene
and is characterized by the development of
various types of cancers by early adulthood
o These are caused by mutations in the
second copy of p53

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Inactivation of Some Tumor
Suppressor Genes Leads to Genetic
Instability

• Genetic instability refers to the fact that

mutation rates in cancer cells are
thousands of times higher than normal

• This state can arise in several ways

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Defects in mitosis

• Genetic instability can

arise from defects that
cause disruptions in
chromosome sorting
during cell division

• This results in
aneuploidy (abnormal
number of
chromosomes)

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• Cancer cells may exhibit defects in the
mitotic spindle checkpoint, which
normally prevents anaphase until all the
chromosomes are correctly attached to
the spindle

• Loss of this checkpoint due to mutations

in the genes that regulate it, e.g., Mad,
Bub, can lead to chromosome mis-
segregation

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Gatekeepers and caretakers

• Tumor suppressor genes such as RB, p53, etc.

are called gatekeepers
o Their loss directly opens the gates to
excessive proliferation and formation of
tumors

• Genes involved in DNA repair and chromosome

sorting are called caretakers
o They help to maintain genetic stability

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Cancers Develop by the Stepwise
Accumulation of Mutations Involving
Oncogenes and Tumor Suppressor
Genes

• Sequencing studies show that a given type of

cancer typically involves mutations in 50–75
genes

• A few of these are mutated frequently in

samples from different people, affecting about a
dozen different pathways

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