Essential

Cell Biology
Fourth Edition

Book Chapter 18; Page: 603-640

Syllabus Chapter 9
Carcinogenesis: Regulation of Cell cycle;
Oncogenes and Tumor Suppressor Genes.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Copyright © Garland Science 2010
 Maximize Your Learning
• Grasp your Syllabus
• Listen to the lecture Attentively
• Take notes
• Read Chapter in advance
• Consult Books vs. notes vs slides
• Think carefully!!
• Ask Questions
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 Asking As Many Questions as Possible
• Raise Your Hands !!
• Write down your questions
• Stay back after the class to get your answers
• In addition to office hours stop by office
• Email using your MEC ID
• You must try to take Notes, If you miss, then
follow up after the class.

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 Office Hours

Mon- Thursdays
2:00 PM-2:30 PM
AB1 Building/1638 Bedford Ave
Room 403D
718-270-6191
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 Focus is the Word
• What is the Color of the wall on you left?
a) White
b) Blue
c) Yellow
d) Red

• The color of the wall on the left is Pink. True or False

• What is the Color of the wall on your left?
Does not matter much whether the
question is MCQ, True or false
or short answer question
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
 Objective
• How cells divide?
• What are the Steps involve in cell cycle
• How Cancer Develops
• What are Proto-oncogenes,
tumor suppressor, Cyclin-dependent kinase
And Cyclins

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 Every organisms has a tendency to grow
But in their own way!!

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 Deficiency in the Removal of Old Cells
& Abrupt Cell Division Have Potential
to Cause Cancers Including Prostate Cancer

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 Replication Plays a Major Role in Development

Copyright
Figure 6-20 © 2005 Pearson
Essential CellEducation,
Biology (©Inc.Garland
publishingScience
as Benjamin Cummings
2010)
Cells that do not divide or are not ready to divide stay
in G0 phase

Non dividing cells like

Neuronal cells

Moderately dividing
Cells like intestinal
Linings

Regularly dividing cells

Like: Skin, hair follicle
https://www.youtube.com/watch?v=lf9rcqifx34
https://www.youtube.com/watch?v=Q6ucKWIIFmg And Bone Marrow cells

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
 Effective Terminologies
• Proto-Oncogene
• Oncogene (Mutant of Proto-oncogene)
• Tumor Suppressor
• Checkpoints

• Acetylation on amino acid Lysine

• Methylation on amino acid Lysine
• Phosphorylation on Serine, Threonine & Tyrosine
• Ubiquitination on amino acid Lysine

• Cyclin-dependent Kinases and Cyclins

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 A multistep model for the development of colorectal cancer

Colon

1 Loss of tumor-
suppressor 4 Loss of
Colon wall gene APC (or 2 Activation of tumor-suppressor
other) ras oncogene gene p53

Normal colon Small benign 3 Loss of Larger benign 5 Additional Malignant tumor
epithelial cells growth (polyp) tumor- growth (adenoma) mutations (carcinoma)
suppressor
gene DCC

Characteristics of cancer cells:

1. Loss of contact inhibition
2. Loss of saturation density
3. Independent of the presence of growth factor.
4. Telomerase gene is activated
5. APC: Anaphase Promoting Complex: in normal cells its promote exit from mitotic cycle

DCC: Deleted in Colon Cancer

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 Few Concepts:

Saturation density:
Saturation density refers to the maximal population density achieved by a cell type grown under
particular in vitro culture conditions. Transformed/cancer cells generally grow to a higher
saturation density than normal cells. For example: normal brain cells grow slowly as compared the
gliomas.

Contact Inhibition:
Human cells exhibit normal cellular behavior and mediate their growth and proliferation via
interplay between environmental nutrients, growth factor signaling, and cell density. As cell
density increases and the culture becomes confluent, they initiate cell cycle arrest and
downregulate proliferation and mitogen signaling pathways regardless of external factors or
cellular metabolism. This property is known as contact inhibition of proliferation and is essential
to proper embryonic development, as well as tissue repair, differentiation, and morphogenesis.
Cancerous cells typically lose this property and thus divide and grow over each other in an
uncontrolled manner even when in contact with neighboring cells.

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Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
 The Control of Cell Cycle Chapter 18
The continuity of life is based on the reproduction of cell

Mitosis 10% time

Cytokinesis

Interphase- 90% time

Interphase consists of:

1. G1 Phase: Produce proteins, organelles.
2. S phase: Synthesis of DNA.
3. G2 Phase: Cell becomes bigger; produce more proteins,
organelles; completes preparation for cell division.

The frequency of cell division in different types of cells is different:

Skin, bone marrow: divide throughout life

Liver: maintain ability to divide

Nerve, muscle: lose ability to divide once matured.

The cell cycle is regulated by molecular control system.

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 Cell Cycle Control System
The timing and rate of cell division in a plant or animal is:
1) Different in different parts of body.
2) Crucial for growth, development, and maintenance.

How cell cycle is controlled ?

*understand normal growth and development.
*understand how cancer cells manage to escape the usual controls

The cell cycle is regulated by a molecular control system.

Checkpoints in the cell cycle control system ensure that key processes in the cycle occurs in
the proper sequence.

Control system are of two general types: Can be compared with

regulation of function of
Internal. Synthesis of molecules and organelles. washing machine.
External. Growth factor binding to receptor.

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 Evidence for Cytoplasmic Signals

In early 1970s:
•Cell cycle is driven by specific molecular signals present in the
cytoplasm.

•Two cells in different phases can be fused to form a single cell with
two nuclei.

•S and G1 phase: G1 nucleus immediately enters S phase.

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 The Cell Cycle Clock: Cyclin and Cyclin-dependent Kinases
To understand how cell cycle checkpoints work, we first
need know what kind of molecules control cell cycle.
Two main type cell cycle control molecules:

I. Cyclin-dependent Kinases (CDKs)

II. Cyclins

Protein kinases are enzymes that activate or inactivate other proteins by

phosphorylation. They are present at constant concentration in the cell.

Cyclin (protein): concentration changes with stages of cell cycle.

Because of the requirement of cyclin, the kinases are called cdk (cyclin-dependent
kinase)

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 The Cell Cycle Control System Depends on Cyclin-dependent Kinases

Pages 608-611
Different Cyclin-Cdk complexes trigger different steps in the cell cycle

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 Molecular Mechanisms that Regulate Cell Cycle

CDK and Cyclin are not needed all the time but only during when the
cells are undergoing division. Hence, after they perform their function
they are degraded by UBIQUITINATION. UBIQUITINATION IS A
POST_TRANSLATION MODIFICATION THAT OCCUR ON AMINOACID
LYSINE
How concentration of cyclin reduces in the cell ?

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 The Multistep Model of Cancer Development
• Normal cells are converted to cancer cells: More than one somatic mutation is
required to produce cancer.
– By the accumulation of multiple mutations affecting proto-oncogenes and
tumor-suppressor genes

Colorectal cancer: 135, 000 new cases per year in the USA
60, 000 death per year

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 Design a rational cancer therapy based of oncogenic signaling pathway

How gleevec works ?

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 Cancer causing genes are classified into two groups:

1. Stimulating cell proliferation:

Oncogenes are cancer-causing genes
• Proto-oncogenes are normal cellular genes that code for proteins
that stimulate normal cell growth and division

• A DNA change that makes a proto-oncogene excessively active

– Converts it to an oncogene, which may promote excessive
cell division and cancer
Proto-oncogene
DNA

Translocation or transposition: Point mutation

Gene amplification: Point mutation
gene moved to new locus, within a control
multiple copies of the gene within the gene
under new controls element

New Oncogene Oncogene

promoter

Normal growth-stimulating Normal growth-stimulating Normal growth-stimulating Hyperactive or

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protein in excess protein in excess protein in excess
 2. Tumor-Suppressor Genes

• Tumor-suppressor genes
– Encode proteins that inhibit cell division

Oncogene product Tumor suppressor gene product

A balance between the signal produced by proto-oncogene and

tumor suppressor gene product is maintained in normal cells.

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 Interference with Normal Cell-Signaling Pathways
• Many proto-oncogenes and tumor suppressor genes
– Encode components of growth-stimulating and growth-inhibiting pathways,
respectively
Oncogene product Tumor suppressor gene product
Tumor suppressor gene product

Normal
Cancer Tumor suppressor gene product

Cancer

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 Molecular model

Gleevec
Gleevec occupies active site of
Kinase and blocks oncogenic signal.

Kinase

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If mammalian cells receive a go-ahead signal at the G1 checkpoint, they will
A) move directly into telophase.
B) complete the cycle and divide.
C) exit the cycle and switch to a non-dividing state.
D) show a drop in Maturation Promoting Factor concentration.
E) complete cytokinesis and form new cell walls.

Cells that are in a non-dividing state are in which

phase?
A) G0
B) G2
C) G1
D) S
E) M

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What causes the decrease in the amount of cyclin at a specific point in
the cell cycle?
A) an increase in production once the restriction point is passed
B) the cascade of increased production once its protein is
phosphorylated by Cdk
C) the changing ratio of cytoplasm to genome
D) its destruction by ubiquitins
E) the binding of PDGF to receptors on the cell surface

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 • Study the following Figure
• In the figure above, mitosis is represented by which number?
• A) I
• B) II
• C) III
• D) IV
• E) V

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G1 is represented by which number(s)?
A) I and V
B) II and IV
C) III
D) IV
E) V
F) II

Which number represents DNA synthesis?

A) I
B) II
C) III
D) IV
E) V

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 Which number represents the point in the cell cycle during which the
chromosomes are replicated?
A) I
B) II
C) III
D) IV
E) V

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Which of the following is true concerning cancer cells?
A) They do not exhibit density-dependent inhibition when growing in culture.
B) When they stop dividing, they do so at random points in the cell cycle.
C) They are not subject to cell cycle controls.
D) B and C only
E) A, B, and C

Which of the following is (are) true concerning cyclin-dependent kinase (Cdk)?

A) Cdk is inactive, or "turned off," in the presence of cyclin.
B) Cdk is present throughout the cell cycle.
C) Cdk is an enzyme that attaches phosphate groups to other proteins.
D) Both A and B are true.
E) Both B and C are true.

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