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An important basic and advanced course of life science

Cellular and
Molecular Biology:
Concepts and
Experiments

Department of Biotechnology
Zhi Huang (黄峙), Ph.D & Prof.
Email: thsh@jnu.edu.cn, Ph: 13678988403, qq:1547461148
Chapter 12 Cancer

Learning Objectives:
1. The biology of cancer
2. The causes of cancer
3. The genetics of cancer;
4. New strategies for combating cancer.
Introduction
 Cancer is a genetics disease. The genetic alterations that
lead most cancers arise in the DNA of a somatic cell, and
result in cancer cells proliferation uncontrollably, producing
malignant tumors that invade surrounding healthy tissue.
 Cancer is not an inherited disease, because the genetic
defect of an inherited disease is present in the
chromosomes of a parent and is transmitted to the zyogte.
 If a tumor remains localized, the disease can usually be
treated and cured by surgical removal of it.
 Malignant tumors tend to metastasize, that is, to spawn
cells that break away from the parent mass, enter the
lymphatic or vascular circulation, and spread to distant sites
in the body where they establish lethal secondary tumors
(metastases) that are no longer amenable to surgical
removal.
 Because of cancer impact on human health and the hope
that a cure might be developed, cancer has been the focus
of a massive research effort for decades.
Figure 12.1 The invasion of normal tissue by a growing
tumor. The metastasized melanosarcoma (in red) is
invading the normal liver tissue.
Figure 12.2 The estimated number of new cancer cases and
deaths in the U.S.A in 1997.
Figure 1. Ten Leading Cancer Types for the Estimated New Cancer Cases
and Deaths by Sex, United States, 2012.

CA: A Cancer Journal for Clinicians


Volume 62, Issue 1, pages 10-29, 4 JAN 2012 DOI: 10.3322/caac.20138
http://onlinelibrary.wiley.com/doi/10.3322/caac.20138/full#fig1
12.1 The Biology of Cancer
Loss of growth control is the most important characteristic of
a cancer cell, as described at the cellular level.

Growth properties
of normal and
cancerous cells.
Normal cells grow
in a culture dish
until they cover the
surface as a
monolayer (a,b).
Malignant cells
typically grow in
multilayered
clumps, or foci (c,d)
The phenotype of a cancer cell
Aneuploidy is the most striking alterations in the nucleus of
cancer cells. Normal cells maintain their diploid chromosome

Karyotype of a cell from a breast cancer line


 The most striking morphological changes in the cytoplasm
of a cancer cell involves the cytoskeleton.
a, These fibroblasts had
been infected with a
temperature-sensitive
tumor virus and cultured
at the higher, restrictive
temperature (39 oC) at
which the protein that
transforms the cells is not
functional. The growth
properties and
arrangement of MTs are
normal. b-d, Cells from
the same culture shown
in (a) that were grown for
5, 24 and 48h at the
lower, permissive
temperature at which the
transformed phenotype is
expressed.
A comparison of the MT cytoskeleton in control and transformed cell cultures.
Tumor antigen is an antigenic substance produced in tumor
cells, i.e., it triggers an immune response in the host. Tumor
antigens are useful in identifying tumor cells and are potential
candidates for use in cancer therapy.
Tumor-Specific Antigens (TSA), which are present only on
tumor cells and not on any other cell and Tumor-Associated
Antigens (TAA), which are present on some tumor cells and
also some normal cells.
 Cancer cells can also be distinguished from normal cells by
their motility in culture.
 Cancer cells growing in culture are much less dependent on
the presence of serum, which provides growth factors such
as epidermal growth factor and insulin.

The effects of serum deprivation on the gorwth of normal


and transformed cells.
12.2 The Causes of Cancer
Environmental agent and the development of cancer.
Carcinogenic chemicals exposure and viruses infection alter
the genome, transforming normal cells into cancer cells.

The mechanism
of action of
chemical
carcinogens.
12.3 The Genetics of Cancer
Malignant transformation requires more than a single
genetic alteration. The development of a malignant tumor,
termed as tumorigenesis, is a multistep process
characterized by a progression of genetic alterations in a
single line of cells that makes the cells increasingly less
responsive to the body’s normal regulatory machinery and
better able to invade normal tissues.

Detection of abnormal cells in a Pap smear. a, Normal


squamous epithelial cells of the cervix. b, Abnormal cells from
a case of carcinoma in situ.
One of a variety of possible sequences of genetic
changes in a cell lineage that can lead to the development
of colon cancer.
APC (adenomatous polyposis coli) is a protein-coding gene,
which encodes a tumor suppressor protein that acts as an
antagonist of the Wnt signaling pathway.
The name 'Ras' is an abbreviation of 'Rat sarcoma', reflecting
the way the first members of the protein family were
discovered. All Ras protein family members belong to a class
of protein called small GTPase, and are involved in
transmitting signals within cells.
DCC gene (deleted in colorectal carcinoma) a gene normally
expressed in the mucosa of the colon but reduced or absent in
a small proportion of patients with colorectal cancer.
Tumor-suppressor genes and oncogenes:
brakes and accelerators
A tumor suppressor gene, or antioncogene, is a gene that
protects a cell from one step on the path to cancer.
Mutation of these genes cause a loss or reduction in its
function, the cell can progress to cancer, usually in
combination with other genetic changes.
The loss of these genes may be even more important than
proto-oncogene/oncogene activation for the formation of
many kinds of human cancer cells.
Tumor suppressor genes can be grouped into categories
including caretaker genes, gatekeeper genes, and
landscaper genes; the classification schemes are evolving as
medicine advances, learning from fields including molecular
biology, genetics, and epigenetics.
Functions of tumor suppressor genes or more precisely, the
proteins for which they code:
• Repression of genes that are essential for the continuing of
the cell cycle.
• Coupling the cell cycle to DNA damage. As long as there is
damaged DNA in the cell, it should not divide. If the damage
can be repaired, the cell cycle can continue.
• If the cell damage cannot be repaired, the cell should initiate
apoptosis (programmed cell death) to remove the threat it
poses for the greater good of the organism.
• Some proteins involved in cell adhesion prevent tumor cells
from dispersing, block loss of contact inhibition, and inhibit
metastasis. These proteins are known as metastasis
suppressors.
• DNA repair proteins are usually classified as tumor
suppressors as well, as mutations in their genes increase the
risk of cancer.
An oncogene is a gene that has the potential to cause
cancer. In tumor cells, they are often mutated or expressed at
high levels.
Activated oncogenes can cause cells designated for
apoptosis to survive and proliferate instead.
Most oncogenes require an additional step, such as
mutations in another gene, or environmental factors, such as
viral infection, to cause cancer.
Since the 1970s, dozens of oncogenes have been identified
in human cancer. Many cancer drugs target the proteins
encoded by oncogenes.
A proto-oncogene is a normal gene that can become an
oncogene due to mutations or increased expression. The
resultant protein may be termed an oncoprotein. Examples
of proto-oncogenes include RAS, WNT, MYC, ERK, and
TRK.
Activation of proto-oncogene:
• A mutation within a proto-oncogene, or within its
regulatory region
• An increase in the amount of a certain protein
• A chromosomal translocation
Contrasting effects of mutations in tumor suppressor genes
(a) and oncogenes (b).
Activation of a proto-oncogene to
an oncogene.
A model for the function of p53. (a) Cell division does not
normally require the involvement of p53. (b) the DNA damage
results in the increasing of p53 expression and acts either to
arrest the progression of the cell through G1 or to direct the
cell toward apoptosis. (c) If the p53 gene are inactivated, the
cell loses the ability to arrest the cell cycle or commit the cell to
apoptosis following DNA damage. As a result, the cell either
dies from mitotic failure or continues to proliferate with genetic
abnormalities that may lead to the formation of malignant
growth.
12.4 New strategies for combating Cancer

Immunotherapy
Gene therapy
Inhibiting the activity of cancer promoting
proteins
Inhibiting the formation of new blood
vessels (angiogenesis)
Angiogenesis and tumor growth.
The response of a solid tumor
grown in mice to treatment with
angiogenesis inhibitors.

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