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200 µm. LE 12-2b. Growth and development. 20 µm. LE 12-2c. Tissue renewal. Types of Cells. ProliferationDifferentiation Highly differentiated cells: Quiescent cells: Highly mitotic cells:. How to determine the cycle?. Experiment 1. S. G 1. LE 12-13a. S. S. - PowerPoint PPT Presentation
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LE 12-2b
Growth and development
200 µm
LE 12-2c
Tissue renewal
20 µm
Types of Cells
• Proliferation Differentiation
• Highly differentiated cells:
• Quiescent cells:
• Highly mitotic cells:
How to determine the cycle?
LE 12-13aExperiment 1
S
S S
G1
When a cell in the S phase was fused with a cell in G1, the G1 cell immediately entered the S phase—DNA was synthesized.
LE 12-13bExperiment 2
G1M
M M
When a cell in the M phase was fused with a cell in G1, the G1 cell immediately beganmitosis—a spindle formed and chromatin condensed, even though the chromosome had not been duplicated.
Mitosis and Cancer
• Common and severe
• Some form strikes 1/3; 20% death; 20% health care costs
• Not a single disease
• Early detection and treatment is vital
cell divisionneoplasmtumor
invadeneighboring tissue
metastasis
LE 12-18a
Cells anchor to dish surface anddivide (anchorage dependence).
When cells have formed a completesingle layer, they stop dividing(density-dependent inhibition).
If some cells are scraped away, theremaining cells divide to fill the gap andthen stop (density-dependent inhibition).
25 µmNormal mammalian cells
LE 12-18b
Cancer cells do not exhibitanchorage dependenceor density-dependent inhibition.
Cancer cells25 µm
The genetic nature of cancer
• The clonal nature of cancer– Analyzing the cancer and normal cells– Most happen later in life
• Proto-oncogenes and oncogenes
• Recessive oncogenes and tumor suppressor genes
LE 12-19a
Tumor
Glandulartissue
A tumor grows from asingle cancer cell.
Cancer cells invadeneighboring tissue.
LE 12-19b
Cancer cell
Bloodvessel
Lymphvessel
Metastatictumor
Cancer cells spreadthrough lymph andblood vessels toother parts of thebody.
A small percentageof cancer cells maysurvive and establisha new tumor in anotherpart of the body.
Searching for Oncogenes
• Cell cycle regulatory genes
• A lot of cancer are associated with DNA virus
• Some cancers are familial
• In vitro mutagenesis on cultured cells
• Loss of heterozygocity
Some Oncogenes• Both viral AND cellular
• src (Rous sarcoma v.): Prototype of a family of membrane associated tyrosine kinases– over expressed or activated in cancer
Kinases: abl (abelson murine leukemia v.)trk (human colon carcinoma v.)
GTPase: ras (rat sarcoma v.)Transcription factors: fos, myc (chicken sarcoma v.)EGF: erb A (avian erythroblastosis v.)
EGF: epithelialPDGF: platelet - derivedCSF: colony stimulatingFGF: basic fibroblast
Some Familial Cancers
• Rb
• familial polyposis coli
• Wilms Tumor
• familial breast cancer
• Li- Fraumeni familial cancer
EGF
EGFR-P
Quiescent Cell Division
P53 p53-p
P21
CDK2-p21Cyclin E
CDK2Cyclin E
CyclinA
Rb-pRb
ras
fosJun
D-cyclin, CDK 2/4/6
RbE2F
E2FEnzymes for DNA synthesis
G1 S
Figure 9.71. Multiple nuclei2. Lost adhesion3. Irregular cell shape4. Vessel invation
Therapy:1. Vessel growth inhibitor2. Nucleotide analog
Figure 9.8a
Protection against cancer:
1. Apoptosis2. Immunity3. Telomeres
Cancer Protection
• Immunity
• Apoptosis
normalincreased growth
adenoma I adenoma II adenoma III
5q gene loss ras mutation ch 18 loss
carcinoma metastasis
ch 17
p53
other ch
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