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Neoplasia

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A Multi step Process. Protooncogenes Oncogenes ... normally expressed in C cells of the thyroid, adrenal medulla, and parathyroid cell precursors ... – PowerPoint PPT presentation

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Title: Neoplasia


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Neoplasia
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  • Neoplasia is the result of
  • 1. Non-lethal cellular damage
  • one target ? Certain genes
  • A Multi step Process
  • Protooncogenes ? Oncogenes
  • Retroviruses (called acute transforming viruses)
    V-onc
  • Contain unique transforming sequences v-onc
  • Cause rapid induction of tumors in animals
  • All v-onc genes have normal cellular homologs
  • Insertion mutagenesis C-onc
  • Insert a slow transforming virus next to a
    proto-oncogene in a normal cell
  • Cellular oncogenes (c-onc) induce a structural
    change in the cellular gene

3
Protooncogenes Oncogenes
Protooncogenes
Oncogenes
Proteins
oncoprotein
No need of Growth Factors
Growth Factors (Hormones etc.)
Normal Growth
Malignant Growth
Oncoprotein ?similar functions as their normal
counterparts but make cells self-sufficient to
grow
4
Normal Cellular counterpart of Genes Homologous
to Oncogenes1. Growth Factors2. Growth Factor
Receptors3. G Proteins4. Kinases Tyrosine
Cyclin dependent (major ones)5. Gene Regulatory
Phosphoprotein6. Transcription
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2
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1. Oncogenes Growth Factors
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  • Protooncogenes Oncogenes
  • 2. Growth Factor receptors (GFR) as oncogenes
  • Mechanism
  • Mutant GFR are in state of persistent
    dimerization activation without binding to GF
  • deliver continuous mitogenic signals to the cell
  • RET proto-oncogene
  • Neurotrophic factor
  • normally expressed in C cells of the thyroid,
    adrenal medulla, and parathyroid cell precursors
  • Mutations ? MEN types 2A and 2B and familial
    Medullary thyroid carcinoma
  • Point mutations in the RET protooncogene
  • In extra cellular domain ? MEN 2A
  • In cytoplasmic catalytic domain ? MEN 2B
  • C-erb B2 (EGF-R2)
  • Amplified in carcinomas of breast, ovary

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  • Protooncogenes Oncogenes
  • 3. Signal- transducing proteins? Oncogenes
  • point mutation of GTP-BINDING RAS proto-oncogene
  • Found in approximately 10-20 of all human tumors
  • single MC abnormality of dominant oncogenes in
    human tumors
  • Related to TGF, PDGF, and CSF-1
  • Also related to CDKs in regulation of cell cycle
  • Non receptor-associated tyrosine kinases
  • c-abl gene of ch.9 translocated fused with
    bcr gene ch. 22 potent tyrosine kinase activity
    ( CML, AML)
  • 4. Transcription proteins ?Oncogenes
  • Myc MC involved in human tumors
  • Others ?Myb, Jun, Fos
  • Oncogenic versions of myc gene
  • Over expression sustained transcription
    neoplastic transformation
  • Translocation Seen in Burkitt lymphoma
  • Amplification breast, colon, lung other Ca.
  • N-myc amplification in Neuroblastomas and small
    cell cancers of lung
  • L-myc amplificationSeen in small cell cancer of
    the lung
  • 5. Cyclin D genes changes Seen in mantle cell
    lymphoma, breast, liver and esophagus cancers
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