Cell cycle and cancer

Sadava, 11.2 Eukaryotic cell division control; 11.6 How do

cells die, 11.7 Unregulated cell division and cancer 15.2
Mutations that lead to genetic diseases
Cell cycle (version 2)
Most cells are not
growing/dividing
they are in G0
Transition from G0 to
G1 is regulated by
growth factors
restriction point
Cells exit cycle and
go back to G0 and
become post-mitotic
differentiated cells
 Growth factors = mitogens
key proteins need to
exit G0
bind to receptor on cell
surface
Induce synthesis of G1
cyclin-CDK complexes
[kinases] among www.fhcrc.org
other things
Figure 9.6 Cyclin-Dependent Kinases and Cyclins Trigger Transitions in the Cell Cycle

The restriction point in

G1 is a decision point
beyond which the rest of
the cycle is inevitable
Progress past the
restriction point depends
on (RB) retinoblastoma
protein.
RB normally inhibits the
cell cycle, but when
phosphorylated, becomes
inactive and no longer
blocks the restriction
point.

Proteins such as p21, p53, p16 and RB that

normally block the cell cycle are known as tumor
suppressors.
Figure 11.22 Apoptosis: Programmed Cell Death

External signals (or absence of signals)

cause membrane proteins to change shape
and activate enzymes called caspases
hydrolyze proteins of membranes
Cancer
 Cell changes in cancer cells

High cell density leads

to hypoxia

Carcinoma epithelial cell tumours

Sarcoma mesoderm (muscle, connective tissue)
17.15 Oncogene Products Stimulate Cell Division
17.17 Tumor Suppressor Gene Products Inhibit Cell Division
 Stem cells

Sadava, Chapter 19.2 Is cell differentiation irreversible? 19.3

Role of gene expression in cell differentiation [both only in
part]
 Stem Cell
Self-
Apoptosis
Renewal

Differentiation
Stem cells are ideally suited for tissue
regeneration and allogeneic transplantations.
They can undergo self-renewal and differentiation
- this is unique feature of stem cell
As differentiation proceeds, cells lose capacity to
self-renew W.L. Stanford
Figure 19.6 Two Ways to Obtain Pluripotent Stem Cells

Some
protocols
use cMyc

Need cytokines/growth
factors here
 Hematopoietic stem cells

Blood cells have limited life span a few days (in most cases); 120
days for erythrocytes
1 in 104 bone marrow cells; best defined system because of success
in bone marrow transplantation (after irradiation/chemotherapy)
 Stromal cell = mesenchymal stromal cell
SCF binds to c-kit on HSC

HSC = hematopoeitic stem cell

Hematopietic stem-cell niche (bone marrow)