PRESENCE in altered or excessive forms contributes to cancer
Mutated forms lead to over-active or too much protein
Involved in growth control
Tumour Suppressor Genes:
ABSENCE can contribute to cancer
Restrain cell growth and division
Often involved n inherited predisposition to cancer
II. HOW ARE ONCOGENES INDENTIFIED?
Knock in and knock out
Oncogenes: “A gene that causes the transformation of normal cells into cancerous tumour cells”,
also defined as “Mutated and/or over-expressed version of normal gene, that in a dominant
fashion releases the cell from normal growth restraints”
Oncogenes gains a function:
- A proto-oncogene is the wild-type allele (normal gene) of an oncogene
- Activating mutation of proto-oncogene creates the oncogene
- One allele usually only affected = DOMINANT
III. HISTORICAL EVIDENCE
1911: Rous isolated virus from spontaneous chicken sarcomas
1914: Theodore Boveri experimented on the development of double-fertilised sea-urchin
eggs and later suggested that malignant tumours might be result of a certain abnormal
condition of chromosomes, which may arise from the multipolar mitosis.
1960: Nowell & Hungerford – evidence form casual role for genomic rearrangement
1969: Huebner & Todaro – proposed viral genes: integrated into genome; dominant
/activated; malignant transformation
Stehelin et al., - demonstrated the RSV contained sequence not found in related, but non-
transforming retrovirus. Viral sequence was related to sequence in DNA of normal chicken
IV. MECHANISMS OF TRANSFORMATION BY RETROVIRUSES
, We can identify oncogenes through retroviruses
Humans do not have many viruses that cause cancers but more in animals and other species
V. DNA TUMOUR VIRUSES: ‘viral oncogenes’
SV40 Large T antigen: binds and inactivates p53 – growing evidence of SV40 in brain cancers,
NHL, lymphoma, and mesothelioma
Adenovirus E1A: binds pRb and immortalises cells
E1B (55K) inactivates p53
HPV E6: interacts with p53 and activates telomerase
E7: interacts with pRb
- HPV 16, 18, 31, 33, 45 found in >99% of all cervical cancer
- Vaccination for HPV to prevent cervical carcinoma
VI. CANCER HALLMARKS
Q&A: Which of the following statements are true of oncogenes?
a. Proto-oncogenes are the result of mutations in oncogenes
b. Both alleles need to be mutated for oncogenic function to be acquired
c. Mutations causing oncogenes usually result in dominant activities
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