Learning Topic 1 - Proto-Oncogenes & Oncogenes

Question 1

What are Proto-oncogenes?

Answer 1

• Normal genes, participate in pathways leading to normal cell growth, division & development.

Question 2

What can Proto-oncogenes be converted into?

Answer 2

• They can be converted into oncogenes.

Question 3

What are Oncogenes?

Answer 3

• Genes that can induce neoplasticism transformation in normal cells.

Question 4

What are the 2 types of Oncogenes?

Answer 4

1 - Viral Oncogenes: Found in viruses + can cause cancer.

2 - Cellular oncogenes: Activated versions of Porto-oncogenes (normal genes).

Question 5

What are the 6 functions of Proto-Oncogenes?

Answer 5

These genes encode proteins that are:

1. Growth factors
2. Growth factor receptors
3. Signal transduction proteins
4. Transcription factors
5. Cell cycle regulators
6. Regulators of Apoptosis

Question 6

What does the general mechanism of activation of Proto-oncogenes to Oncogenes involve?

Answer 6

• increase in amount of normal gene product.

OR

• production of abnormal gene product.

Hence, it is due to QUANTITATIVE or QUALITATIVE changes in the normal Proto-oncogene.

Question 7

What are the 4 mechanisms that convert Proto-oncogenes to Oncogenes called?

Answer 7

1. Viral Insertion
2. Point Mutation
3. Amplification
4. Chromosomal Translocation

Question 8

Describe the mechanism of Viral Insertion :

Answer 8

• Cell infected virally causing viral DNA to be inserted into host DNA
• Viral DNA either inc. efficiency of cellular gene promoter or alters cellular gene by causing mutation within the gene.
• Results in either inc. amount of product or an altered protein which can result in CANCER DEVELOPMENT.

Question 9

Describe the Mechanism of Point Mutation :

Answer 9

• Mutation occurs, leading to production of protein w/ altered function.

Question 10

Give an example of Point Mutation :

Answer 10

• K-RAS in lung cancer.
• K-RAS is a Proto-oncogene. It mutates into RAS Oncogene.
• RAS Oncogene codes for a protein that differs from the normal gene product by one Amino Acid.

Question 11

Describe the mechanism of Amplification :

Answer 11

• Occurs when a gene or gene sequence is “amplified” or is increased hundreds of times in copy number.

Question 12

Where is the amplified DNA located?

Answer 12

• Within the chromosome of the cell

OR

• Located on extrachromosomal elements known as “double minute.”

Question 13

What does amplification lead to? What is particularly affected?

Answer 13

• Excessive increase in amount of normal gene product.

- Regulatory molecules, which can have drastic effects on normal growth regulation of a cell.

Question 14

Give an example of Amplification:

Answer 14

• N-mye in neuroblastoma
• N-mye is a Proto-oncogene that is amplified into the myc Oncogene.
• myc Oncogene, which codes for a transcription factor, is found amplified in many neuroblastomas.
• The highest degree of amplification of myc often correlates with more advanced stages of the cancer.

Question 15

Describe the mechanism of Chromosomal Translocation:

Answer 15

• A gene is translocated to a different position in the genome
• Leading to an altered expression of the gene

OR

• The production of a fusion protein that has altered functions.

Question 16

Give an example of Chromosomal Translocation:

Answer 16

• bcr-abl in chronic myeloid leukaemia CML
• Translocation between chromosome 9 & 22 produces the fusion protein bcr-abl.
• The fusion protein bcr-abl has defective protein kinase activity in normal control.
• The abl (abelson) Proto-oncogene encodes a tyrosine-specific protein kinase.
• The Bcr-Abl fusion oncoprotein has a permanent protein kinase activity responsible for oncogene cancer activity.

Question 17

Where can the src gene be found? What is it’s cellular counterpart called?

Answer 17

• Found in Rous Sarcoma Virus & is called v-src

- The cellular counterpart is called c-src & is present in living organism

Question 18

What is the normal function of the Src protein?

Answer 18

• It is a Protein Tyrosine Kinase, which means it PHOSPHORYLATES TYROSINES ON PROTEINS
• Normally found in cytosol

Question 19

How does this go wrong in cancer?

Answer 19

• Alterations in src lead to inc. in Src kinase activity.
• Activated Src will phosphorylate other proteins in the cell, altering their activity.
• This causes changes in signal transduction pathways leading to cell cycle deregulation & cancer.

Question 20

What does Ras do normally?

Answer 20

• Encode guanine-nucleotide binding proteins.
• The normal activity of the Ras proteins is controlled by GTP or GDP binding
• Such that they alternate between active (GTP-bound) & inactive (GDP-bound) states.

Question 21

What does RAS activation lead to?

Answer 21

• Enhanced signal transduction through Raf-1 serine-threonine kinase & the Early Response Kinase (ERK1 & ERK2)
• Subsequent induction of transcription of immediate early genes in the nucleus ( FOS, JUN, EGR1 )

Question 22

What happens in cancer? (Ras)

Answer 22

• Ras is permanently activated
• Raf is activated
• MAP Kinase cascade us switched on
• Increased expression of target genes - leading to cancer

Question 23

How is RAS activated?

Answer 23

• Certain base mutations

- Over expression ( gene amplification)