7. Cellular proliferation

Question 1

What determines the size of a cell population in adults?

Answer 1

• Depends on rate of:
  i) cell proliferation, regulated by proto-oncogenes
  ii) cell differentiation
  iii) cell death by apoptosis

(i.e. increased cell numbers seen with increased proliferation or decreased cell death)

Question 2

How is cell proliferation controlled?

Answer 2

• Largely by chemical signals (e.g. hormones) from the microenvironment, which either stimulate or inhibit cell proliferation.
• When a signalling signalling molecule binds to a receptor, it results in modulation of gene expression (proto-oncogenes).
• Receptors usually in cell membrane but can be in cytoplasm or nucleus (e.g. steroid receptors).

Question 3

What can chemical signals make a cell do?

Answer 3

1. survive - resist apoptosis
2. divide - enter cell cycle
3. differentiate - take on specialised form and function (permanent exit from cell cycle)
4. die - undergo apoptosis

Question 4

How can increased tissue growth be promoted by modifying the cell cycle?

Answer 4

1. shortening the cell cycle

2. conversion of quiescent (G0) cells to proliferating cells by making them enter cell cycle

Question 5

What are the phases of the cell cycle?

Answer 5

Interphase:

• G1 - gap 1, cell growth and protein synthesis
• S - DNA synthesis/replication
• G2 - gap 2, preparation for division

Question 6

Can cells with damaged DNA replicate?

Answer 6

In physiological state, no, as cell cycle progression controlled by checkpoints which monitor DNA damage and level of DNA replication.

• G1/S checkpoint: checks for DNA damage before replication
• G2/M checkpoint: checks for DNA damage after replication
• Restriction (R) point towards end of G1 is most critical checkpoint - point of no return.

Question 7

Which is the most commonly altered checkpoint in cancer cells?

Answer 7

R point

Question 8

What is the result of checkpoint activation?

Answer 8

Cell cycle is suspended and:

• DNA repair mechanisms triggered
• or apoptosis if DNA cannot be repaired

controlled by p53

Question 9

Which proteins regulate cell cycle progression?

Answer 9

Cyclins and cyclin-dependent kinase (CDK) enzymes -particularly regulate G1/S transition

1. CDKs activated by binding to cyclins
2. activated CDKs phosphorylate proteins (e.g. retinoblastoma susceptibility protein) that are critical for progression to next cell cycle stage

Question 10

How do some growth factors promote tissue proliferation via cyclin-CDKs?

Answer 10

1. some stimulate cyclin production

2. some prevent production of CDK inhibitors (which tightly regulate activity of cyclin-CDK complexes)

Question 11

How many times can cells divide?

Answer 11

Hayflick limit (due to telomere degeneration from lack of telomerase) = 61.3 divisions

Question 12

During which phase of the cell cycle are cells responsive to mitogenic GFs and TGF-B?

Answer 12

G1 until R point