Cell cycle and cancer

Question 1

What is neoplasia?

Answer 1

A new growth of cells not under normal physiological control.

Question 2

What is a tumour?

Answer 2

A tumour is formed by an excessive uncontrolled proliferation of cells as a result of an irreversible genetic change which is passed from one tumour cell to its progeny.

Question 3

What is apoptosis?

Answer 3

Programmed cell death.

Question 4

What is hyperplasia?

Answer 4

Is an increase in the size of an organ as a result of cell proliferation eg. uterus in pregnancy.

Question 5

What is hypertrophy?

Answer 5

Is an increase in the size of an organ due to an increase in the size of the constituent cells eg. left ventricle of the heart in hypertension.

Question 6

What are benign tumours?

Answer 6

They usually stay localised at their site of origin. They rarely lead to a patients death.

Question 7

What are malignant tumours?

Answer 7

They are able to invade and spread to different sites=cancer. Can lead to a patients death.

Question 8

What is dysplasia?

Answer 8

Synonymous with intraepithelial neoplasia. Disordered epithelial cell growth, characterised by loss of architectural orientation and development of cellular atypia.

Question 9

What is metaplasia?

Answer 9

A change from one type of differentiated tissue to another. Often the resulting tissue is better adapted to the environment. Can be a precursor of dysplasia and cancer.

Question 10

Modes of tumour spread

Answer 10

• Local invasion
• Lympathic spread
• Blood spread
• Transcoelomic spread (across the peritoneal cavity). Common in ovarian and stomach cancers and malignant mesothelioma.

Question 11

What is a paraneoplastic syndrome?

Answer 11

Due to inappropriate hormone secretion by a tumour eg. many carcinomas produce parathyroid hormone related protein (PTHrP) which activates osteoclasts and hence raises serum calcium.

Question 12

What is grading?

Answer 12

Histologically assessing how closely the cancer cells resemble normal tissue.

Question 13

What is staging?

Answer 13

Seeing how far the cancer has spread eg. TNM staging system. (Tumour, Node, Metastasis).

Question 14

What are cyclin-dependent kinases?

Answer 14

Serine/threonine kinases that require the binding of a cyclin for full activity. They regulate progression through the cell cycle and their activity must be tightly regulated.Kinases add phosphate groups to its substrate.

Question 15

What are cyclins?

Answer 15

Unstable activator proteins that are up- or down- regulated depending on the phase of the cell cycle.

Question 16

What are cyclin- dependent kinase inhibitors?

Answer 16

CKIs are small proteins that block cyclin/CDK activity ether by forming an inactive complex or by acting as a competitive CDK ligand. Examples: p21, p27, p57.

Question 17

What happens in prophase?

Answer 17

Chromatin condensation, nucleolus disappears, centrioles move to poles.

Question 18

What happens in pro-metaphase?

Answer 18

Nuclear membrane dissolves. Chromosomes attach to microtubules and begin moving.

Question 19

What happens in metaphase?

Answer 19

Spindle fibres align the chromosomes along the middle of the cell nucleus (metaphase plate).

Question 20

What happens in anaphase?

Answer 20

Paired chromosomes separate and move to opposite sides of the cell.

Question 21

What happens in telophase?

Answer 21

Chromatids arrive at opposite poles of the cell. New membranes form around daughter nuclei. Chromosomes decondense. Spindle fibres disperse.

Question 22

What is progression to M phase dependent on?

Answer 22

Dependent on cdk1/cyclin B (MPF), Cyclin B levels start to rise in G2 in preparation. Also known as maturation promoting factor (MPF).

Question 23

What are checkpoints?

Answer 23

Point in eukaryotic cell division cycle where progress through the cycle can be halted until conditions are suitable for the cell to proceed. Important in cell monitoring.

Question 24

What is the restriction point?

Answer 24

The point in G1 after which the cell no longer requires growth factors to complete the cell cycle and it commits to cell division. This is dependent on the accumulation of cyclin D and occurs 2-3 hours prior to the initiation of S-phase. Retinoblastoma (Rb) protein acts as the gatekeeper at the restriction point.

Question 25

What is p53?

Answer 25

A tetrameric transcription factor that inhibits cell cycle progression and allows for DNA repair. It promotes apoptosis (high levels result in apoptosis).

Question 26

What is the M/spindle checkpoint?

Answer 26

A surveillance mechanism that delays anaphase onset until all the chromosomes are correctly attached to the mitotic spindle.

Question 27

What are tumour suppressor genes?

Answer 27

If TSG have mutations in them this results in function and allows cell cycle to proceed, possibly leading to cancer RB and p53 are examples.

Question 28

What is RB?

Answer 28

Retinoblastoma is a TSG found at the restriction checkpoint. It inhibits cell cycle progression until appropriate conditions are met. ‘brakes’ on E2F activity (S phase gene expression).

Question 29

What does cyclinD/CDK4/6 do?

Answer 29

Promotes cell cycle progression past the restriction point by phosphorylating and thus inhibiting RB, which allows E2F mediated, S-phase gene transcription.

Question 30

What is a philadelphia translocation?

Answer 30

A chromosomal rearrangement which causes a bcr (chrom. 22)-abl (chrom. 9) hybrid gene which leads to chronic myeloid leukemia. abl gene is a intracellular tyrosine kinase so can be treated with tyrosine- kinase inhibitors ie. Imatinib (Gleevec).

Question 31

What does p53 do at low levels and high levels?

Answer 31

At low levels, it switches on p21 cdk inhibitor which causes cell cycle arrest. At high levels, it will switch on pro-apoptotic genes.

Question 32

What is E2F?

Answer 32

A transcription factor that is necessary for the induction of synthesising proteins required for S Phase. It is normally kept inactivated by the presence of the RB protein. Cyclin D/CDK 4,6 inactivates RB.

Question 33

What is G0?

Answer 33

Quiescence. This is when the cell is not actively proliferating and needs an external stimulus to re-enter the cell cycle. Still may be very active in terms of carrying out its differentiated function.

Question 34

What are proto-oncogenes?

Answer 34

Normal cellular genes that code for proteins needed to normal cell division/proliferation. Certain activating mutations can turn them into oncogenes which can then bypass the need for extracellular growth signals snd so lead to uncontrolled cell division/proliferation.

Question 35

How do oncogenes work?

Answer 35

They either code for an hyperactive version of the protein product or they make the normal protein product but in abnormal quantities, at the wrong time or in the wrong cell type. Which of these depends on the type of mutation and where it occurs in the gene.

Question 36

What are telomeres and how do they work?

Answer 36

They prevent end-to-end fusion of chromosomes. The are repeating TTAGGG sequences added to the end of chromosomes by telomerase. Constitutive telomerase expression may lead to immortalisation of cells.

Question 37

What happens in hereditary retinoblastoma?

Answer 37

One allele of the RB1 gene is mutated or deleted in the germ cells. The other allele is lost via a somatic mutation later on. The hereditary form features bilateral, multifocal retinal involvement and typically manifest early, before the age of 1.

Question 38

What happens in sporadic retinoblastoma?

Answer 38

More common than hereditary. Is often unilateral and unifocal in origin. The age of onset is usually alter, between the ages of 1 and 2.

Question 39

What does germline mutation of p53 cause?

Answer 39

Li-Fraumeni syndrome, in which multiple cancers develop at a relatively young age (younger than 45). p53 is inactivated in around 50% of all human cancers.