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What is Cancer?What is Cancer?Definit ion: Definit ion: 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).
Cellular Transformation►When the cell fails to respond to suchsignals, it is “out of control”, and can continue to
divide.
►The daughter cells will also continue to divide.
►Ultimately, might result in cancer.
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.
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.)
Genes and Cancer►Mutations that result in cancer typically occurin 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)
Tumor Viruses For most viruses: Genome Viral Proteins
Replication Lysis Progeny virions
Lytic Life Cycle
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!
Tumor Viruses
Transformation:
Loss of growth control Abil ity to form tumors - viral genes interfere with
control of cell replication.
Similar Mechanisms
VIRAL TRANSFORMATIONThe changes in the biological functions of a cell
that result from REGULATIONof the cell’s metabolism by viral genes and that
confer on the infected cell certain properties characteristic of
NEOPLASIAThese changes often result from the integration
of the viral genome into the host cell DNA.
TRANSFORMATION Among the many altered properties of the
TRANSFORMED CELL are:►Loss of growth control ( loss of contact
inhibit ion in cultured cells).►Tumor formation.►Mobility.►Reduced adhesion.►Transformed cells frequently exhibit
chromosomal aberrations.
DNA Tumor Viruses Papil loma Viruses:• Cause natural cancers in animals.
• Cause benign warts.
• Ubiquitous.
• Epitheliotropic - most human tumors are malignancies of epithelial cells.
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.
DNA Tumor Viruses Adenoviruses
►Highly oncogenic in animals.
►Only part of virus integrated.
►Always the same part.
DNA Tumor Viruses Herpes VirusesConsiderable 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.
DNA Tumor Viruses Hepatit is B Virus
DNA genome RNA Provirus DNA genome
RNA polymerase II Reverse transcriptase Host enzyme Viral enzyme
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
RNA Tumor Viruses A normal retrovirus has 3 genes :
GAG : Internal proteins.ENV: Envelope glycoproteins.POL: Enzymes Reverse transcriptase Integrase Protease
RNA Tumor Viruses Groups of Retroviruses• OncovirinaeTumor viruses and similar
• LentivirusesLong latent periodProgressive chronic diseaseVisna HIV
• Spumavirinae
RNA Tumor Viruses Proto-oncogeneA 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.
RNA Tumor VirusesThe discovery of the acutely transformingretroviruses that contain v-oncs explains how
cancers may arise as a result of infection.
These viruses cause rapid cancer in animals inthe laboratory.