Chapter8(2) Abnormal cell proliferation,
differentiation and related diseases
What is cell proliferation?
• Cell proliferation is a process of cell
division and regeneration, which results
in an increase in the cell number with
exact passages of genetic information to
their daughter cells.
What is cell cycle?
• Cell cycle is defined as a period
Proliferation
from the end
of one division to the
of eukaryotic
cell division of a
beginning of next
proliferative cell.
DNA replication
Phases of the cell cycle
G1 phase
S phase
G2 phase
M phase
Phases of the cell cycle
G1 phase
S phase
G2 phase
M phase
DNA Cell Cycle Analysis
For adult
• Cycling cells with continuous division
Embryo cells, hematopoietic cells
• Differentiated cells
Cardiac cells, nerve cells
• Most cells
Skin fibroblasts, SMCs, VECs, cells of internal organs
Control of the Cell Cycle
The passage of a cell through the cell cycle is
controlled by proteins in the cytoplasm. These
protein are:
• Cyclins
• Cdks (Cyclin-dependent kinases)
• CKIs(Cyclin dependent kinase inhibitor )
• APC (anaphase-promoting complex)
Control of the Cell Cycle
The passage of a cell through the cell cycle is
controlled by proteins in the cytoplasm. These
protein are:
• Cyclins
• Cdks (Cyclin-dependent kinases)
• CKIs(Cyclin dependent kinase inhibitor )
• APC (anaphase-promoting complex)
Cyclins
Kinase
complex
Vertebrate
Yeast
Cyclin
CDK
Cyclin
CDK
G1-CDK
Cyclin D*
CDK4 、6
Cln 3
CDK1(CDC28)
G1/S-CDK
Cyclin E
CDK2
Cln 1、2
CDK1(CDC28)
S-CDK
Cyclin A
CDK2
Clb 5、6
CDK1(CDC28)
M-CDK
Cyclin B
CDK1(CDC2) Clb 1-4
CDK1(CDC28)
Cyclins
Kinase
complex
Vertebrate
Yeast
Cyclin
CDK
Cyclin
CDK
G1-CDK
Cyclin D*
CDK4 、6
Cln 3
CDK1(CDC28)
G1/S-CDK
Cyclin E
CDK2
Cln 1、2
CDK1(CDC28)
S-CDK
Cyclin A
CDK2
Clb 5、6
CDK1(CDC28)
M-CDK
Cyclin B
CDK1(CDC2) Clb 1-4
CDK1(CDC28)
Cyclins
Kinase
complex
Vertebrate
Yeast
Cyclin
CDK
Cyclin
CDK
G1-CDK
Cyclin D*
CDK4 、6
Cln 3
CDK1(CDC28)
G1/S-CDK
Cyclin E
CDK2
Cln 1、2
CDK1(CDC28)
S-CDK
Cyclin A
CDK2
Clb 5、6
CDK1(CDC28)
M-CDK
Cyclin B
CDK1(CDC2) Clb 1-4
CDK1(CDC28)
Cdks
Kinase
complex
Vertebrate
Yeast
Cyclin
CDK
Cyclin
CDK
G1-CDK
Cyclin D*
CDK4 、6
Cln 3
CDK1(CDC28)
G1/S-CDK
Cyclin E
CDK2
Cln 1、2 CDK1(CDC28)
S-CDK
Cyclin A
CDK2
Clb 5、6 CDK1(CDC28)
M-CDK
Cyclin B
CDK1(CDC Clb 1-4
2)
CDK1(CDC28)
Cdks
Steps in the cycle
CKIs
• Kip (Kinase inhibition protein)：
P21waf1/cip1 (cyclin inhibition protein 1)、
P27kip1(kinase inhibition protein 1)、
P57kip2
• Ink4(Inhibitor of cdk 4):
P16Ink4a、P15Ink4b
P18Ink4c、P19Ink4d
CKIs
• Kip (Kinase inhibition protein)：
P21waf1/cip1 (cyclin inhibition protein 1)、
P27kip1(kinase inhibition protein 1)、
P57kip2
• Ink4(Inhibitor of cdk 4):
P16Ink4a、P15Ink4b
P18Ink4c、P19Ink4d
Degradation of cyclin B
Degradation of cyclin B
Cell cycle checkpoints
Regulation of cell cycle by extracellular signal
Growth
factors
Tumor
• Overexpression of cyclins
• Overexpression of Cdks
• Deactivation of CkIs
• Abnormity of checkpoints
Tumor
• Overexpression of cyclins
• Overexpression of Cdks
• Deactivation of CkIs
• Abnormity of checkpoints
Psoriasis
What is cell differentiation?
• Cell differentiation is a cellular events
that gives rise to different kinds of cells
with the specialized morphology,
metabolism and physiological functions
from the cells of the same origin.
What is cell differentiation?
What is cell differentiation?
• Cell differentiation is a cellular events
that gives rise to different kinds of cells
with the specialized morphology,
metabolism and physiological functions
from the cells of the same origin.
Control of cell differentiation
– Genomic level
– Transcription/post-transcription levels
– Extracellular factors
House-keeping genes
DNA
methylation↓
Differentiation-related genes
DNA
methylation↓
Tissue-specific genes
Control of cell differentiation
– Genomic level
– Transcription/post-transcription levels
– Extracellular factors
Tumor
• Low differentiation
• Dedifferentiation
• Retrodifferentiation
• Divergent differentiation
• Induced differentiation
Pulmonary fibrosis
Vessel injury
Thrombin
Myofibroblast
(+)
Fibroblast
Deposit of collagen in lung
Teratoma