Biology of cancer, lecture 2 tumor viruses,oncogenes,tsgs
Upcoming SlideShare
Loading in...5
×
 

Biology of cancer, lecture 2 tumor viruses,oncogenes,tsgs

on

  • 6,572 views

 

Statistics

Views

Total Views
6,572
Views on SlideShare
6,555
Embed Views
17

Actions

Likes
3
Downloads
638
Comments
1

3 Embeds 17

https://nccu.blackboard.com 12
http://www.linkedin.com 4
https://www.linkedin.com 1

Accessibility

Categories

Upload Details

Uploaded via as Adobe PDF

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel

11 of 1

  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
  • u guys have some gud stuff in here!
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

    Biology of cancer, lecture 2 tumor viruses,oncogenes,tsgs Biology of cancer, lecture 2 tumor viruses,oncogenes,tsgs Presentation Transcript

    • Tumor Viruses Oncogenes & Tumor Supressor genes Adapted from The Biology of Karobi Moitra (Ph.D) Cancer First Edition NCI Frederick , NIH Cancer Inflammation Program Robert A. Weinberg Human Genetics Section Chapter 3, 4 & 7 Frederick MD. MD. Copyright © Garland Science 2007
    • Peyton Rous and Rous Sarcoma Virus (RSV) 1910 1966 Figure 3.1 The Biology of Cancer (© Garland Science 2007)
    • 1909 Rous’s Protocol for inducing breast sarcomas in chicken Viruses can cause cancer in chickens ! Figure 3.2 The Biology of Cancer (© Garland Science 2007)
    • The Virion (virus particle) of RSV and other related viruses: RNA viruses (retroviruses) can cause cancer Figure 3.4a The Biology of Cancer (© Garland Science 2007)
    • Structure of the RSV genome ALV = Avian leukosis virus Oncogene Figure 3.19 The Biology of Cancer (© Garland Science 2007)
    • The Double Helix
    • RNA vs DNA
    • The Virion (virus particle) of RSV and other related viruses: RNA viruses (retroviruses) can cause cancer Figure 3.4a The Biology of Cancer (© Garland Science 2007)
    • RNA to DNA Reverse transcription with the enzyme reverse transcriptase
    • The flow of genetic information- the central dogma
    • Murine (mouse) Leukemia Virus particles budding from an infected cell Figure 3.4b The Biology of Cancer (© Garland Science 2007)
    • Normal cells can be converted into tumor cells (transformation) Figure 3.7a The Biology of Cancer (© Garland Science 2007)
    • Normal cells can be converted into tumor cells (transformation) : RSV can transform infected cultured cells (in a petri dish) An RSV induced Foci CALTECH: Dulbecco,Rubin & Temin Figure 3.5 The Biology of Cancer (© Garland Science 2007)
    • Some viruses can transform normal cells 1910 1966 Nobel prize in Physiology and medicine
    • DNA Viruses can also induce cancer Shopes virus Richard Shope Figure 3.9a The Biology of Cancer (© Garland Science 2007)
    • HPV = Human papilloma virus - A DNA tumor virus Figure 3.9b The Biology of Cancer (© Garland Science 2007)
    • Table 3.1 The Biology of Cancer (© Garland Science 2007)
    • Oncogenes were first discovered in viruses and called v-oncs , viral oncogenes
    • Oncogenes & Proto-oncogenes
    • Genes and Cancer Viruses Chemicals Radiation Heredity Chemicals (e.g., from smoking), radiation, viruses, and Chromosomes heredity all contribute to the development of cancer by are DNA triggering changes in a cell’s genes molecules
    • Oncogenes or tumor genes are genes with potential properties for the induction of neoplastic transformation (either in natural or experimental conditions) (Duesberg 1980) Normal cellular genes with the potential to become oncogenes are called proto-oncogenes
    • Proto-oncogene Oncogene
    • Proto-Oncogenes and Normal Cell Growth Normal Growth-Control Pathway Growth factor Receptor Signaling enzymes Transcription factors Cell nucleus DNA Cell proliferation Oncogenes are related to normal genes called proto-oncogenes that encode components of the cell’s normal growth-control pathway. Some of these components are growth factors, receptors, signaling enzymes, and transcription factors. Growth factors bind to receptors on the cell surface, which activate signaling enzymes inside the cell that, in turn, activate special proteins called transcription factors inside the cell’s nucleus. The activated transcription factors “turn on” the genes required for cell growth and proliferation.
    • Normal cell Normal genes regulate cell growth Oncogenes Cancer cell accelerate cell growth and division Oncogenes are genes whose PRESENCE in Mutated/damaged oncogene certain forms and/or overactivity can stimulate the development of cancer.
    • Oncogenes or tumor genes are genes with potential properties for the induction of neoplastic transformation (either in natural or experimental conditions) (Duesberg 1980) The word oncogene comes from the word ‘onkos ‘ meaning tumor
    • When a proto-oncogene becomes activated it is called an oncogene
    • Proto-oncogene Oncogene
    • When an oncogene becomes activated it might cause cancer Proto-oncogene -> oncogene -> other steps -> cancer
    • Activation of Oncogenes 1. Mutation a. Insertional mutagenesis b. Point mutagenesis 2. Amplification 3. Translocation
    • Mutation : A mutation is a permanent change in the DNA sequence of a gene. Mutations in a gene's DNA sequence can alter the amino acid sequence of the protein encoded by the gene.
    • 1a. Insertional Mutagenesis ALV provirus may become integrated with the c-myc oncogene ALV switches on c-myc Figure 3.23b The Biology of Cancer (© Garland Science 2007)
    • Activation of oncogenes 1b. Mutagenesis of oncogenes Altered polypeptides produced by mutant oncogenes could be related to the origin of some human tumors
    • Activation of oncogenes Mutation responsible for H-ras oncogene activtion Human bladder cancer oncogene - 12th codon of H-ras ,mutation converts glycine codon to valine codon Figure 4.10 The Biology of Cancer (© Garland Science 2007)
    • Activation of oncogenes 2. Amplification of oncogenes More than one copy of a gene: Amplification
    • Activation of oncogenes The N-myc gene is often amplified in human childhood neuroblastomas FISH - showing amplification of N-myc to produces HSR’s homogeneous staining regions (chromosome 2) Figure 4.11a The Biology of Cancer (© Garland Science 2007)
    • How are oncogenes amplified? Double minute chromosomes
    • Activation of oncogenes 3. Translocation A chromosome translocation is a chromosome A karyotype is the number and appearance abnormality caused by rearrangement of parts of chromosomes in the nucleus of a between nonhomologous chromosomes. A gene eukaryote cell fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer.
    • Burkitts lymphoma t(8;14) the c-myc gene is placed under the control of the enhancer sequence of an immunoglubulin gene Figure 4.13a The Biology of Cancer (© Garland Science 2007)
    • Reciprocal translocations between human Chr 9 (abl) and 22 (bcr) Fusion protein Bcr-abl oncogene formation gives rise to acute lymphocytic leukemia (ALL),chronic myelogenous leukemia (CML) or chronic neutrophillic leukemia (CNL) Figure 4.15a The Biology of Cancer (© Garland Science 2007)
    • Activation of Oncogenes 1. a. Insertional mutagenesis b. Point mutagenesis 2. Amplification 3. Translocation
    • Tumor Suppressor Genes
    • Tumor Suppressor Genes Tumor suppressor genes are normal genes whose ABSENCE can lead to cancer i.e. Tumor suppressor genes protect the cell
    • Tumor Suppressor Genes - Tumor suppressor genes are normal genes whose ABSENCE can lead to cancer i.e. Tumor suppressor genes protect the cell Normal cell Normal genes prevent cancer Remove or inactivate tumor suppressor genes Cancer cell Damage to both genes leads to cancer Mutated/inactivated If a pair of tumor suppressor genes are either tumor suppressor genes lost from a cell or inactivated by mutation, their functional absence might allow cancer to develop
    • Tumor Suppressor Genes Act Like a Brake Pedal Tumor Suppressor Gene Proteins Growth factor Receptor Signaling enzymes Transcription factors Cell nucleus DNA Cell proliferation Tumor suppressor genes are a family of normal genes that instruct cells to produce proteins that restrain cell growth and division. Since tumor suppressor genes code for proteins that slow down cell growth and division, the loss of such proteins allows a cell to grow and divide in an uncontrolled fashion. Tumor suppressor genes are like the brake pedal of an automobile. The loss of a tumor suppressor gene function is like having a brake pedal that does not function properly, thereby allowing the cell to grow and divide continually.
    • Tumor suppressors act similar to the ‘brakes’ of a car (analogy)
    • p53 Tumor Suppressor Protein Triggers Cell Suicide p53 protein Normal cell Excessive DNA damage Cell suicide (Apoptosis) One particular tumor suppressor gene codes for a protein called “p53” that can trigger cell suicide (apoptosis). In cells that have undergone DNA damage, the p53 protein acts like a brake pedal to halt cell growth and division. If the damage cannot be repaired, the p53 protein eventually initiates cell suicide, thereby preventing the genetically damaged cell from growing out of control.
    • pRB - Tumor suppressor gene From R Bernards
    • Petite arm (small) NLM
    • Retinoblastoma occurs when pRB is mutated (inactivated) or sometimes deleted Figure 7.4b The Biology of Cancer (© Garland Science 2007)
    • Inherit mutant allele Figure 7.7 The Biology of Cancer (© Garland Science 2007)
    • Deletion of a part of Chromosome 13 in a retinoblastoma patient Figure 7.10 The Biology of Cancer (© Garland Science 2007)
    • Oncogenes or tumor genes are genes with potential properties for the induction of neoplastic transformation either in natural or experimental conditions (Duesberg 1980) Tumor suppressor genes are normal genes whose ABSENCE can lead to cancer
    • “Never, never, never give up” Winston Churchill 1966 Nobel prize in Physiology and medicine