Chapter 13 Cancer cells
2nd Edition
13.1．Basic knowledge about cancer cell
13.1.1．Cancer types

benign
malignant
（1）Carcinoma
Carcinomas are cancers derived from epithelial (lining) cells, which
cover the surface of our skin and internal organs. This is the most
common cancer type and represents about 80%-90% of all cancer
cases reported.
（2）Adenocarcinoma
Adenocarcinoma refers to carcinoma derived from cells of glandular
origin. One can, for instance, have an adenocarcinoma of the pancreas,
or an adenocarcinoma of the lung. These are very different cancers.
（3）Sarcoma
Sarcomas are cancers of the connective tissue, cartilage, bone, fat,
muscle, and so on.
（4） lymphoma and leukemia, derived from bone marrow and
affects the lymphatic system. In leukaemia, lymphocytes cells do
not mature properly and become too numerous in the blood and
bone marrow. Leukaemias may be acute or chronic. The most
common type is acute lymphoblastic leukaemia (ALL). There are a
number of other less common acute types which may be grouped
together as acute non-lymphoblastic leukaemia (ANLL), this
includes acute myeloid leukaemia (AML).
（5）Myelomas
Myelomas are cancers of specialized white blood cells, involving
the white blood cells responsible for the production of antibodies (B
lymphocytes or B-cells).
Cancer
13.1.2 Basic properties of cancer cells
•
loss of growth control
1) grow and divide in the absence of stimulatory growth
signals and/or in the presence of inhibitory signals.
2) Loss of monolayer character
3) Self secretion
• Dedifferentiation of the cancer cells
• Avoidance of cell death
• The morphological and chemical changes of cancer
cells
1) Decrease of proteins in cell surface and loss of gap
junction.affect cell adhesion and movement (motility).
2) Nuclear changes. Chromosome aneuploidy.
3) Enzyme production. Telomerase.
13.1.3. Angiogenesis and
Metastasis
• Angiogenesis
Tumor cells also need require nutrients and
oxygen in order to grow to a large mass
Angiogenesis is an essential step in the
growth of a tumor
• Tumor metastasis
Bloodstream metastasis
Lymphatic metastasis
Stimulatory growth by self secretion of cancer cells
13.2.1. Stages of Tumor
Progression
•
•
•
•
Hyperplasia
Dysplasia
Carcinoma in situCancer (Malignant tumors)
Figure 20-9 Molecular Biology of the Cell (© Garland Science 2008)

Metastasis of cancer cells
Figure 13-2 Molecular Biology of the Cell (© Garland Science 2008)
13.2.2 The Environmental Factors
of Carcinogenesis
In-vitro Environment
carcinogens （mutagen)
Chemical carcinogens
Radiation carcinogens（Ultra-violet
(UV) radiation
causes point mutations. X-rays ）
Viruses（Oncogenic DNA Viruses ，RNA retroviruses）
In-vivo Environment
Hormone
Immune system
Chronic inflammation
Oxygen Radicals （ reactive oxygen
intermediates, ROI; or
reactive oxygen species, ROS)
Chemical carcinogens
13.3 Tumor genetics
◆ tumor suppressor gene
◆oncogene:An oncogene is any gene that encodes a
protein able to transform cells in culture or to
induce cancer in animals..
●c-onc
●v-onc
◆ proto-oncogene Almost all the oncogenes are
derived from normal cellular genes which is called
proto-oncogenes
The proto-oncogenes
includes
• ① The extracellular signaling molecules,
• ② The membrane receptors for the signal
molecules(e.g.HER-2/neu (erbB-2),
• ③ The growth factor receptor,
• ④ The signal-transduction proteins(e.g. ras and src),
• ⑤ The transcription factors in the nucleus(e.g. myc),
• ⑥ The enzymes that function in DNA replication (for
example, hTERT).
• ⑦ The genes that resist apoptosis and promote survival,
e.g.Bcl-2, a membrane associated protein that functions
to prevent apoptosis
• gain-of-function mutation: proto-oncogene---oncogene
• Functions of oncogenes
• Growth factors
• Growth factor receptors
• Signal tranductors
• Nuclear transcription factors.
• Cell cycle regulators
• Apoptotic resistant factors
proto-oncogene
Oncogene
transformation
Groups of tumor suppressor genes
• Tumor suppressor genes function in many key
cellular processes, mainly grouped in the following 5
classes:
• ① Intracellular proteins that regulate or restrain cell
cycle (e.g.p16 and Rb)
• ② Receptors or signal transducers for secreted
hormones or developmental signals that inhibit cell
proliferation (e.g.TGF)
• ③ Checkpoint-control proteins that arrest the cell
cycle if DNA is damaged or chromosomes are
abnormal (e.g.p53)
• ④ Proteins that promote apoptosis
• ⑤ Enzymes that participate in DNA repair(e.g.BRCA)
 tumor suppressor genes and carcinogensis
◆RB gene is Retinoblastoma susceptible gene,
the transcript is 4.7kb ， encoding 105kDa
protein with 928 aa， which is called P105-RB。
◆ P105-RB play a key role in controlling system
of cell cycle pathway. Dephosphated RB is a
active form and it can inhibite cell propagation.
Mutation of proto-oncogene and tumor suppressor
gene can affect cell propagation.
What is p53 ?
• P53 gene is thought to be a most important
cancer-related gene so far. It encodes 53kDa
phosphated protein, named P53。
•Tumor suppressor gene, located in the short arm
of the human chromosome 17
• 393 amino acids
• Play an important role in cell activity, such as a
transcript factor
•Loss-of-function in most cancer，reason：
mutations in the TP53 gene or binging to viral
proteins or other proteins
p53 history
• Discovered in 1979
• nominated as oncogene in 1983
• Defined as a tumor suppressor gene in 1988
• p53 mutation was founded in tumor in 1989
• 10000 cases mutaions were reported in 1999
• 16000 cases mutaions were reported in 2001
p53：a sensor of multiple forms of stress
function of p53
• When DNA was damaged,
the cell was seizured at
G1->S
• modulating cell apoptosis
p53 mutation
• p53 somatic mutations are found in most types
of sporadic human cancers at various frequencies
(from 20% to 60%)
• p53 mutations may also be inherited in families
with a predisposition to multiple cancers, as in the
Li-Fraumeni syndrome (LFS)
• more than 1700 different mutations have been
described
Mutation frequency statistics
•Mutation concentrated in exon4－9
•Mutation frequency in tumors is high（20%-60%）
•Frequently mutated in CpG region, most GC－TA
•Hot mutaion site: where higher frequency of mutation
happend
p53 mutations in various cancer
p53 mutations in various cancer
The most frequent p53 mutations
P53 and carcinogenesis
The ways to cause genetic
alterations
•
•
•
•
•
•
1) DNA point mutations
2) Alterations of larger amounts of DNA
① Translocations.
② Inversions.
③ Duplications/Deletions.
④ Aneuploidy.
leukemia
The other genetic changes
• Gene amplification
• Loss of heterozygosity (LOH) of tumorsuppressor genes
The way of Proto-oncogene
activated to oncogene
Metastasis
progression of
Colon cancer
Viral oncogene and cancer
◆ cellular oncogene，(c-onc): from
proto-oncogene；
◆ viral oncogene，(v-onc): 100 v-onc
were identified, most of them are
RNA v-onc
The model of origination of
RNA virus oncogene
13.4 The Epigenetic Changes In
Cancer
DNA methylation
some nucleotides in the DNA are modified by the addition
of a methyl (-CH3) group to the base, usually to C in
CpG dinucleotides. Almost half of the known genes have
CpG islands in promoters and the first exon regions.
Methylation of DNA is associated with the inactivation of
that particular region of DNA.
Genomic methylation patterns are frequently altered in
tumor cells, with global hypomethylation accompanying
region-specific hypermethylation events.
Histon acetylation
the histone proteins around which the DNA is
wound become modified by the addition of
acetyl (-CH3CHO) groups. This alteration
leads to a loosening of the DNA:histone
interaction and is associated with increased
gene expression.
This is a reversible modification, which is
carried out by two families of enzymes, the
histone acetyltransferases (HATs), and the
histone deacetylases (HDACs). Because of
their important roles in the regulation of such
events, enzymes that affect histone
acetylation status are increasingly being
associated with tumors.
13. 5. Aberrant Gene Expression
Pattern of Cancer Cells
Because the heterogeneity of cancer, expression profiles
are diverse between normal cells and corresponding
cancer cells and among different types of tumors, even
in different individual of same kind of cancer. Some of
these differences can be correlated with biological
differences between the tumors or diverse of
tumorigenesis; Even though most of the differences can
not be explained, they can provide cancer researchers
with a list of genes look at more closely as potential
targets for therpeutic drugs diagnosis biomarkers.
Molecular Biology of the Cell (© Garland Science 2008)
Figure 13-4 Molecular Biology of the Cell (© Garland Science 2008)
13.6 Cancer Detection and
Diagnosis
• (1) Imaging techniques
• (2) Tumor biomarkers
• (3) Early detection of cancer
1) Protein biomarker detect
2) gene expression pattern in RNA level
3) Genetic test
13.7 Treatment of Cancer
(1) Traditional treatments
(2) New strategies for cancer treatment
1) Immunotherapy
2) Gene therapy
3) Inhibiting the activity of oncogenes
4) Preventing angiogenesis