Cellular + Molecular events in carcinogenesis Flashcards Preview

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Flashcards in Cellular + Molecular events in carcinogenesis Deck (34)
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1
Q

What is the reason for the long interval between exposure to a carcinogen and clinical recognition of the tumour

A

Tumours result from clonal proliferation of single cells

It takes a large time for one cell to grow into a nodule of cells

2
Q

Describe the initiation stage of tumour formation

A
  1. When carcinogens induce a genetic alteration that gives transformed cell neoplastic potential
3
Q

Describe the promotion stage of tumour formation

A
  1. Stimulation of clonal proliferation of the initiated transformed cell
4
Q

Describe the progression stage of tumour formation

A
  1. Process culminating in malignant behaviour characterised by invasion and its consequences
5
Q

How does successive applications of a carcinogen and promotor cause a malignant tumour on a mouse

A
  1. A single application results in a visible tumour if it is followed by repeated painting of the site with the promotor
  2. Carcinogen is the initiator which induces the lesions on the DNA of target cells
  3. Promoter is the one that promotes the growth of the initiated cells - further events lead to malignancy
6
Q

How many genetic alterations are needed to transform a normal cell to a neoplastic cell and what are they

A

Many:

  1. Expression of telomerase
  2. Loss or inactivation of both copies of a tumour suppressor gene to remove inhibitory control of cellular replication
  3. Activation or abnormal expression of oncogenes to self-stimulate cell proliferation
7
Q

How do tumour suppressor gene inactivation and abnormal oncogene expression work together to form neoplastic cells

A

Drive cells from their normal state of regulated growth to deregulated and uncontrolled growth

8
Q

How is genomic instability effected by age

A

Increases with age

9
Q

What are the two types of tumour suppressor genes

A

Caretaker

Gatekeeper

10
Q

What are caretaker genes

A

Maintain the integrity of genome by repairing DNA damage

11
Q

Role of BRCA 1

A

Tumour suppressor caretaker gene involved in DNA repair

12
Q

Role of BRCA2

A

Involved in DNA repair

13
Q

Mutation of BRCA1 and BRCA2 can cause what

A

Breast, prostate and pancreatic cancer

14
Q

What are gatekeeper genes

A

Genes inhibiting the proliferation or promote the death of cells with damaged DNA

15
Q

What is p53

A

Transcription factors that responds to DNA damage

16
Q

Where is p53 found

A

Chromosome 17

17
Q

What are the normal functions of p53

A
  1. Repair of damaged DNA before S phase in the cell cycle by arresting it in G1 until damage is repaired
  2. Apoptotic cells each if there is extensive DNA damage
18
Q

What happens to p53 levels in cells with sustained DNA damage

A

They rise until damage is repaired or cell goes through apoptosis

19
Q

How can p53 lose its function

A

Non-sense mutation - Unreadable
Missense mutation - defective protein

Complexes of normal and mutant p53 prevent normal function

Binding of normal p53 to proteins encoded by oncogenic DNA viruses

20
Q

What syndrome does INHERITED mutation of p53 result in

A

Li-fraumeni syndrome

21
Q

What is RB1

A

Transcriptional regulatory - controls cell cycle G1/S checkpoint

22
Q

What are RB1 associated with

A

retinoblastoma

23
Q

What are retinoblastoma

A

Bilateral Malignant tumours derived from the retina in children

24
Q

When can retinoblastoma become unilateral

A

Sporadic when there’s no family association

25
Q

What usually results in hereditary retinoblastoma

A

gremlin deletion on chromosome 13 where RB1 gene is

Only one further mutational loss is needed in any target retinal cell for a tumour to develop

26
Q

What do sporadic retinoblastoma requires in order for a tumour to develop

A

They have two normal chromosome 13s and require 2 mutations or losses of RB1 in the same cell

27
Q

Where are oncogenes found

A

In oncogenic RNA retroviruses which have th ability to transfer theirs or parts of their genomes to cells they infect

28
Q

How do oncogenic RNA retroviruses infect host cell genomes

A
  1. Reverse transcriptase that enables viral RNA to be reverse transcribed into complementary DNA which is incorporated into genome
29
Q

What are five types of oncoprotein

A
  1. Growth factors
  2. Receptors for growth factors
  3. Signalling mediator with tyrosine kinase activity
  4. Nuclear-binding transcription factor oncoprotein
  5. Signalling mediator with nucleotide binding activity
30
Q

How can oncogenes be activated

A
  1. Mutation resulting in an oncoprotein molecule altered in such a way that it is excessively active
  2. Excessive production of a normal oncoprotein because of gene amplification or enhanced transcription
31
Q

How common is oncogene activation

A

Present in most tumours

32
Q

Describe the translocation mechanism of oncogene activation

A
  1. If an oncogene is translocated from an untranscribed site to a position adjacent to an actively transcribed gene (e.g. in Burkitt’s lymphoma where oncogene is translocated form chromosome 8 to 14 and placed adjacent to one of the immunoglobulin genes
33
Q

What is the point mutation mechanism of oncogene activation

A
  1. E.g. in codon 12 of ras oncogene where substitution of a single base is translated into amino acid substitution causing it to become hyperactive
34
Q

What is the amplification mechanism of oncogene activation

A

Insertion of multiple copies of the oncogene resulting in cellular proliferation stimulated by excessive quantities of the oncoprotein

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