Cancer Biology 1

Question 1

What is the appearance of cells in hyperplastic growth and how do they differ from normal ones? What about dysplastic growth? What is an adenocarcinoma?

Answer 1

They contain excessive number of cells but only deviate minimally from the appearance of normal ones. Dysplastic growth cells the appearance is no longer normal e.g variability in nuclear size and shape. Adenocarcinoma is a tumour forming from glandular structures in the epithelium

Question 2

What changes in milk duct tissues if they become cancerous?

Answer 2

The normal tissue architecture becomes deranged- i.e nuclei become very large and no longer form well-structured ducts and have invaded the strome

Question 3

90% of cancers are carcinomas- they arise from epithelial cells. What two types of cancers are there?

Answer 3

Squamous cell carcinomas and adenocarcinomas

Question 4

What are squamous cells and what are their function?

Answer 4

Flattened cells that protect the epithelium and underlying tissues from the contents of the lumen (e.g intestines) or from the outside world (e.g skin). Mature flattened cells shed from the surface as dead keratinocytes. In these cell carcinomas, the malignant cells can be seen invading the stroma

Question 5

What are glandular cells and what are their function?

Answer 5

Cells in the epithelium that secrete mucopolysaccharides to protect epithelium or to secrete proteins that function within cavities

Question 6

Where do adenocarcinomas arise from and what sort of architecture is seen in these cells?

Answer 6

Glandular cells and the architecture of them are deranged and unorganised- you can grade the cancer on how deranged the tissue is

Question 7

Tumours can arise from many different cell types. Using tumours of the CNS, explain what this means.

Answer 7

They can arise from all three lsyers of the cerebellum- Glandular layer, purkinje cells and molecular layer

Question 8

Many human cancers share the same stages of tumour development and the molecular mechanisms may be common too. How do all cancers start and what is it that makes them ‘monoclonal’?

Answer 8

All start from a single genetic change in a single cell

Question 9

What are driver mutations?

Answer 9

Cancers accumulate many mutations during development and those that are critical for tomourigenesis are called driver mutations

Question 10

What are passenger mutations?

Answer 10

Genetic changes in late-stage tumours that are not associated with tomourigenesis but reflect developing instability of the cancer genome

Question 11

What is apoptosis and does this happen to cancer cells?

Answer 11

When cells break away from the tissue they belong to, they are killed off (apoptosis). Cancer cells do not undergo this so when they break off they contribute to formation of metastasis (spread of cancer to other organs). In addition, cancer cells also secrete enzymes which help invasion of underlying stroma and capillaries

Question 12

Why do cancer cells keep growing when they reach confluence? Do they need as many growth factors as normal cells? Do they grow attached to tissue or is this not needed in a growth medium?

Answer 12

They do not show contact inhibition like other cells (grow over the top of each other).
They also need fewer growth factors than normal cells. Cancer cells often float around in clumps (anchorage-independent growth) unlike normal cells which require attachment to the petridish

Question 13

Cell numbers balance rate of cell proliferation, differentiation, apoptosis and senescence. Describe which can be altered in cancer and give an example of one

Answer 13

All can be altered

E.g Leukemic cells fail to differentiate into a RBC and continue to divide instead

Question 14

Hanahan and Weinberg proposed the ‘Hallmarks of Cancer’. What are these and why were they proposed?

Answer 14

These were proposed as features that usually must be altered in order to produce a full blown cancer:

Evasion of immune attack
block differentiation
Limitless replication
Evasion of apoptosis
Invasion and mestastasis
Sustained angiogenesis

Question 15

Why is cancer seen as a disease of old-age?

Answer 15

Because 6-7 alterations are required for the development of a full blown cancer and these may accumulate over many years

Question 16

What does the Ames mutation test measure? What sort of bacteria was this using? What was the correlation seen?

Answer 16

Quantifies the ability of a certain chemical or substance to induce mutation in a specific bacterial gene.
Bacteria that would not grow on a minimal medium, only with extra histidine supplemented. This is because this strain had a mutation in the enzyme that breaks histidine down. Certain chemicals were tested to see if a mutation was caused to revert it back to the wild type which can grow on minimal medium.
There was a correlation between carcinogenicity (inducing tumours in mice) and mutagenicity (ability to revert back to wildtype)

Question 17

Why was a liver used in the Ames mutation test?

Answer 17

Many things are not carcinogens until our liver breaks them down

Question 18

How did Rous identify the virus that caused sarcomas (malignant tumour) in chickens?

Answer 18

Tumour tissue was ground up and filtered through a fine-pore filter so that bacteria could not pass through. The filtrate was then shown to cause tumours in inoculated young chickens- the virus is an acutely transforming retrovirus (developed in several weeks)

Question 19

Rous Sarcoma Virus (RSV) is also able to transform cultured cells (mimicking tumour cells). What does the loss of contact inhibition lead to on cell monolayers?

Answer 19

A ‘focus’ of cells (clump)

Question 20

ALV was also shown to cause sarcomas in chicken. What is the difference between this virus and RSVs?

Answer 20

ALVs cause cancers after months so it is considered a slow retrovirus (not an acutely transforming retrovirus). This is due to the lack of the ‘src’ gene found in RSV but not ALV. It is a viral oncogene at the 3’ end called v-Src

Question 21

Uninfected chicken DNA was seen to hybridise to radiolabelled v-Src and this was called c-Src. This is found in many uninfected species. What does this tell you about this gene? Is it still considered an oncogene? What is it called when it has integrated into the DNA?

Answer 21

It is a genuine cellular gene which is called a provirus after integration

Question 22

How did SRV virus initially form?

Answer 22

ALV retrovirus (that lacks oncogene) integrated next to c-Src gene, it is possible this gene was picked up as part of its natural lifecycle. It would form part of the transcript and then would by spliced and packaged into a capsid. This would then go on to be highly expressed in cells and cause tumours. Additional mutations would accumulate to increase the tumourigenic activity

Question 23

Give definitions of this terminology:

Cellular proto-oncogenes
Cellular oncogenes
Retroviral transduction
Retroviral oncogenes

Answer 23

Cellular proto-oncogenes are genes within our genome that have the potential to become activated so as to contribute to cancer. These act as normal genes if appropriately regulated
Cellular oncogenes (c-oncs) are when these become activated- this can happen by alteration to their expression levels or to their amino acid sequences
Retroviral transduction refers to the process of picking up cellular proto-oncogenes by a tretrovirus
Retroviral oncogenes (v-onc) are genes contribute to cancer causing properties in a virus

Question 24

Are acutely transforming retroviruses associated with humans?

Answer 24

No, mainly chickens, rats and mice

Question 25

What are slow retroviruses and do they possess an oncogene in their genome? What are some examples?

Answer 25

Viruses which cause cancers a long time after infection
They do not have oncogenes in their genome
Examples include ALV, MLV and MMTV

Question 26

How do slow retroviruses cause cancer if they do not have a v-onc present in their genome? What is this process called?

Answer 26

They integrate next to a cellular proto-oncogene and this leads to high levels of that genes expression therefore contributing to cancer. It does not pick up the proto-oncogene (doesn NOT transduce) but just activated its expression in situ. This process is called insertional mutagenesis

Question 27

Amplification of genes in human cancers can be seen in breast cancer and human neuroendocrinal tumours. How can this over expression of cellular oncogenes be visualised?

Answer 27

Using FISH

Question 28

What are Homogenously Staining Regions (HSRs)?

Answer 28

Chromosomal segments with various lengths and uniform staining intensity after G banding. This type of aberration is also known as Copy Number Gains or Amplification.

Question 29

What are regions of gene amplification in human tumours that frequently appear as small, independently-replicating extrachromosomal particles termed?

Answer 29

Double minutes (DMs)

Question 30

Is gene amplification a good or poor porognosis?

Answer 30

A poor prognosis e.g amplification of N-myc in childhood neuroblastoma

Question 31

In breast cancer, amplification of HER2/Neu oncogenes are seen. What does this gene encode?

Answer 31

A growth factor receptor (this can be a target for the drug Herpceptin)

Question 32

What can chromosome translocation lead to?

Answer 32

The overexpression of a proto-oncogene or to the production of abnormal oncogenic proteins product- the outcome depends on the location of the break points in respect to the protein-coding regions of the affected genes

E.g In Burkitt’s lymphoma, break point is outside the protein coding region and this causes overexpression od c-myc oncogene

In Chronic Myelogenous Leukaemia, break point is within coding regions which leads to a chimeric protein has increased biological activity