Cancer arises from normal cells whose nature is permanently changed, causing them to multiply rapidly and not be subject to normal control. Oncogenes are genes capable of transforming normal cells into cancerous cells and result from mutations of normal proto-oncogenes. Both DNA and RNA tumor viruses can transform cells through integration into the host cell DNA, which results in loss of growth control and tumor formation. Retroviruses contain oncogenes (v-onc) that are homologous to cellular proto-oncogenes (c-onc) and can induce transformation after mutation or other changes to the cell's genome.

1. ViralViral
OncogenesisOncogenesis

2. What is Cancer?What is Cancer?
Definition:Definition: Any disorder of cell growth that results in invasion
and destruction of surrounding healthy tissue by abnormal cells.
Cancer cells arise from normal cells whose nature is permanently
changed.
They multiply more rapidly than healthy body cells and do not
seem subject to normal control by nerves and hormones.
They may spread via the bloodstream or lymphatic system to
other parts of the body, where they produce further tissue damage
(metastasis).

3. Regulation of Cell Division In NormalRegulation of Cell Division In Normal
CellsCells

4. Cellular Transformation
►When the cell fails to respond to such
signals, it is “out of control”, and can continue to
divide.
►The daughter cells will also continue to divide.
►Ultimately, might result in cancer.

6. Carcinoma (Skin Cancer)Carcinoma (Skin Cancer)
Basal skin carsinoma.Basal skin carsinoma.

7. Sarcoma (In bone , Muscle or otherSarcoma (In bone , Muscle or other
Soft Tissue)Soft Tissue)

8. Leukemia (Cancer of the bone marrow)
Too manyToo many leucocytes are produced.

9. Lymphoma
(cancer of the lymph tissue)

10. Myeloma
(Cancer of The Myeloid Tissue)
Myeloid tissue is where blood forms in the red
bone marrow in vertebrates. It is important in
the immune system.

11. Oncogenes
 A gene that is capable of transforming a normal
cell into a cancerous cell.
 Oncogenes result from the mutation of normal
genes (proto-oncogenes).
 Oncogenes are also seen in oncogenic viruses.
(Viral oncogenes are derived from normal host genes that have
become incorporated into the viral genome and subsequently
undergo mutation.)

12. Genes and Cancer
►Mutations that result in cancer typically occur
in 3 types of genes.
– Proto-oncogenes: (genes whose products
stimulate cell multiplication)
– Tumor-suppressor genes: (genes whose
products inhibit cellmultiplication)
– Mutator genes: (genes whose products ensure
accurate DNA replication and DNA repair)

13. Genes and Cancer
Retinoblastoma

15. Tumor Viruses
For most viruses:
Genome Viral Proteins
Replication Lysis Progeny virions
Lytic Life Cycle

17. Tumor Viruses
Latent Life Cycle
Virus Cell Integration (usually)
Transformation
►Virus-specific proteins expressed - No
mature virus changes in the properties
of host cell – TRANSFORMATION!

18. Tumor Viruses
Transformation:
Loss of growth control Ability to form
tumors - viral genes interfere with
control of cell replication.

19. TRANSFORMATION
►Both DNA and RNA tumor viruses can
transform cells. Integration occurs (usually).

20. Similar Mechanisms
VIRAL TRANSFORMATION
The changes in the biological functions of a cell
that result from
REGULATION
of the cell’s metabolism by viral genes and that
confer on the infected cell certain properties
characteristic of
NEOPLASIA
These changes often result from the integration
of the viral genome into the host cell DNA.

21. TRANSFORMATION
Among the many altered properties of the
TRANSFORMED CELL are:
►Loss of growth control (loss of contact
inhibition in cultured cells).
►Tumor formation.
►Mobility.
►Reduced adhesion.
►Transformed cells frequently exhibit
chromosomal aberrations.

25. DNA Tumor Viruses
Papilloma Viruses:
• Cause natural cancers in animals.
• Cause benign warts.
• Ubiquitous.
• Epitheliotropic - most human tumors are
malignancies of epithelial cells.

26. DNA Tumor Viruses
Epidermodysplasia
verruciformis
Papilloma virus

27. DNA Tumor Viruses
Polyoma Viruses
• Simian virus 40 - juvenile hamster sarcomas,
transformation.
• Polyoma - mouse leukemia, in vitro
transformation.
• Human polyomas (JC and BK) – monkey
sarcoma , transformation
PROGRESSIVE MULTIFOCAL
LEUKOENCEPHALOPATHY
Polyoma virus transforms cells when the
genome is incomplete.
Early functions are necessary.

28. DNA Tumor Viruses
Adenoviruses
►Highly oncogenic in animals.
►Only part of virus integrated.
►Always the same part.

29. DNA Tumor Viruses
Herpes Viruses
Considerable evidence for role in human
cancer.
• Some very tumorigenic in animals.
• Viral DNA found in small proportion of tumor
cells: “hit and run”.
► Epstein-Barr Virus.
► Burkitt’s Lymphoma.
► Nasopharyngeal cancer.
► Infectious mononucleosis.
► Transforms human B-lymphocytes in vitro.

30. DNA Tumor Viruses
Hepatitis B Virus
DNA genome RNA Provirus DNA
genome
RNA polymerase II Reverse transcriptase
Host enzyme Viral enzyme

31. RNA Tumor Viruses
RNA Genome – (Retroviruses)
RNA-dependent DNA Polymerase encoded by
virus.
RNA Genome DNA Genome Integrates RNA Genome
Reverse transcriptase Integrase Host RNA
polymerase II
Virus Virus Host

32. RNA Tumor Viruses
A normal retrovirus has 3 genes :
GAG : Internal proteins.
ENV: Envelope glycoproteins.
POL: Enzymes
Reverse transcriptase
Integrase
Protease

33. RNA Tumor Viruses

34. RNA Tumor Viruses
Groups of Retroviruses
• Oncovirinae
Tumor viruses and similar
• Lentiviruses
Long latent period
Progressive chronic disease
Visna HIV
• Spumavirinae

36. RNA Tumor Viruses
Viral Oncogene
V-onc
Cellular Proto-oncogene
C-onc

37. RNA Tumor Viruses
Proto-oncogene
A cellular (host) gene that is homologous with a
similar gene that is found in a transforming
virus.
A cellular oncogene can only induce
transformation after:
• mutation
• some other change in the cell’s
genome.

38. RNA Tumor Viruses
The discovery of the acutely transforming
retroviruses that contain v-oncs explains how
cancers may arise as a result of infection.
These viruses cause rapid cancer in animals in
the laboratory.

39. RNA Tumor Viruses
ALV can integrate into the host cell genome at
MANY locations but in tumor it is always at the
SAME site (or restricted number of sites).
Suggest tumor arose from one cell.
• Something must be important about this site for
transformation.
• Crucial event must be rare.