1. Cancer Biology Jasmina Makarevic
ATTA-UR-RAHMAN SCHOOL OF
APPLIED BIOSCIENCES (ASAB)
Cancer Biology Jasmina Makarevic
Fall Semester 2016

2. Oncogenes/ Proto-Oncogenes
Def.:
Oncogenes: a cancer-inducing gene
Proto–oncogenes: a normal cellular gene that, upon alteration by
DNA-damaging agents or viral genomes, can acquire the ability to
function as an oncogene.
Tumor-supressor-genes: produce proteins which control the cell-cycle or
lead to apoptosis (program of celullar self-destruction)
loss of these genes leeds to cancer!
Jasmina Makarevic

3. Theory of „HITS“
Knudson hypothesis (multi-hit hypothesis): cancer is the result of accumulated mutations to a cell‘s DNA (Alfred G. Knudson, 1971)
e.g.: If renoblastom is inherited it occures in earlier years. When it is non-inherited at least two „hits“ to occure until it become cancer. That is why you get it in older age. (Mutations had to occure in both alleles before becoming cancer)
Jasmina Makarevic

4. Two-Hits theoretical curve
Jasmina Makarevic

5. Solid Cancers Colon Cancer: Five hits to achieve an invasive carcinoma
Jasmina Makarevic

6. Chemical Carcinogenesis I
First evidence from Paracelcius in 1567: „wasting deseas of the miners“
And many more after him…
To better understand the connection, scientist began to induce tumors
in animals with chemical substances. In 1915, Katsusaburo Yamagiwa
reported the first succesful induction in a rabbits ear.
Jasmina Makarevic

7. Chemical Carcinogenesis II
Jasmina Makarevic

8. Chemical Carcinogenesis III
Summary statistics (2012)
Chemical Carcinogenesis III
Covalent bond formation between an electrophilic form of the
carconogen and the nucleophilic site in the proteine and
nucleic acids  leeding to mutations
Jasmina Makarevic

9. Important Experimental Proof
Fruit fly genetic: 1927, Hermann Mueller induced mutations in the genom of
Drosophila melanogaster by exposing these flies to x-ray.
In the 1940s many other chemicals used in the World War I
were also found to be mtagenic
These findings caused several geneticists to speculate
that cancer was a disease of mutant genes. Many other
Scientists proofd this in the last 50 years.
But how can we proof the relative mutagenic potencies of a
chemical species?
Jasmina Makarevic

10. The Ames Test Release ist enzymes Chemically activated ,
Summary statistics (2012)
The Ames Test
Release ist enzymes
Chemically activated ,
mutagenic state
Mutant allele, which caused this
Phenotype in Salmonella was
susceptible to back-mutation to a
wild-type allele.
Salmonella has no DNA-
Recovering system
smalle Lipopolysaccharids
Jasmina Makarevic

11. Epidemiologic Studies
Def.: Is the science which studies the patterns, causes and effects of healthand disease conditions in defined populations.
Jasmina Makarevic

12. Tumor Viruses Leading their host to an uncontrolled proliferation!
One of the first experiments: 1911 Peyton Rous:
Jasmina Makarevic

13. Transformed cells forming foci
Jasmina Makarevic

14. Transformed morphology
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15. Conclusion
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16. Onco-Virus
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17. DNA-Virus
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18. Life cycle of an RNA tumor virus like RSV
Jasmina Makarevic

19. Structure of the Rous sarcoma virus genom
Reverse Transcriptase: Enzyme makes DNA complementary copy of an
RNA molecule using the RNA molecule as tamplate
Integrase: Integrate e.g.: retroviral DNA genome into hostecell
Chromosomal DNA
Jasmina Makarevic

20. Making of src-specific DNA
Src-gene = proto-oncogene
Jasmina Makarevic

21. Transforming Retroviruses
Jasmina Makarevic

22. RVS without proto- oncogene? Insertional mutagenesis
ALV (avian leukosis virus)
MLV (murine leukemia virus)
Jasmina Makarevic

23. Outlook
1. Are there bacteria which causes cancer? What is about chronic inflammation?
What happens in the process in cancer initiation, promotion and progression?
Jasmina Makarevic

24. Thank You for Your Attention!
Jasmina Makarevic