Cancer Biology

Question 1

How is tumourogenesis initiated?

Answer 1

Initiated due to environmental carcinogens or viruses

Question 2

How does tumourogenesis occur?

Answer 2

Mutation occurs activating oncogenes and loss of tumour supressors, so proliferation occurs and increases, further mutations then occur and result in a cell with capabilities to become malignant.

Question 3

What changes occur during tumourogenesis?

Answer 3

• uncontrolled cell proliferation
• blocked differentiation
• increased growth capacity
• increased cell motility
• accquired tissue invasion capability
• loss of genomic stability

Question 4

What are the 6 characteristics of cancer?

Answer 4

• Cells acquire autonomous drive to proliferate through activation of oncogenes
• Inactivation of tumour supressor genes that normally inhibit growth
• Evasion of programmed cell death
• limitless replication potential
• Sustained angiogenesis
• Tissue invasion and metastasis

Question 5

How does the cell cycle initiate in cancers?

Answer 5

• Usually cell cycle does not autonomously initiate, normally needs growth factors, signal and Rb proteins.
• In cancer activates autonomously by targetting the molecules above and removes or alters them.

Question 6

What is an oncogene?

Answer 6

A gene whose product is involved in inducing cancer. Most oncogenes are mutated forms of proto-oncogenes involved in the control of cell growth and division.

Question 7

What is a proto-oncogene?

Answer 7

A normal cellular gene that encodes a protein usually involved in regulation of cell growth and proliferation, and when mutated becomes a cancer producing oncogene.

Question 8

What is a tumour supressor gene?

Answer 8

A gene whose encoded protein directly or indirectly inhibits progression through the cell cycle and in which a loss of function mutation is oncogenic.

Question 9

Why is knowledge of cancer molecules important for drug production?

Answer 9

May target mutated oncogenes for different types of cancer.

Question 10

What sort of mutations may a proto–oncogene undergo to become an oncogene and what are their effects?

Answer 10

-Deletion/point mutation: hyperactive protein made in normal ammounts
-Regulatory Mutations: normal protein greatly overproduced
-Gene amplification: normal protein greatly overproduced
-Chromosome rearrangement: nearby regulatory DNA sequence causes normal protein to be overproduced OR
fusion to actively transcribed genes produces hyperactive fusion protein

Question 11

What are examples of oncogenes formed by deletion/point mutations?

Answer 11

• Ras
• BRAF
• EGFR

Question 12

What is an example of an oncogene formed by gene amplification?

Answer 12

HER-2

Question 13

What is the importance of tumour supressor genes in cancer?

Answer 13

In many tumours, they are lost of inactivated, contributing to abnormal proliferation of tumour cells.

Question 14

What are some examples of tumour supressors?

Answer 14

• Rb
• p53
• BRCA-1

Question 15

What is the 2 hit hypothesis?

Answer 15

At least 2 mutational events must occur at the same locus to result in tumourogenesis.

Question 16

Give an example of chromosome rearrangement oncogene (fusion)?

Answer 16

BRC-Abl in many leukemia cases

Question 17

What molecule allows tumours to have limitless replication potential and to be immortal?

Answer 17

Increased expression of Telemorase

Question 18

What molecules may allow tumours to have sustained angiogenesis?

Answer 18

VEGF

Question 19

How are tumours able to become malignant and start spreading?

Answer 19

E-cadherin forms part of adherins junction, often epithelil tissues lose these as they progress to malignancy.
Cell-ECM junctions (integrins) are altered frequently in tumours.
These cells can invade as they produce proteases, an important class of these is MMP's which break down and allow cells to invade and spread.