Oncogenes and Onc-Gene Products Folder Title: Oncogene Updated: April 15, 2010 OncTitle.

Oncogenes and Onc-Gene Products

Folder Title: Oncogene

Updated: April 15, 2010

OncTitle

Examples of Oncogenic RNA Viruses(from Ruddon, 3rd Ed, Table 6.2)

Acute Transforming Viruses

Rous Sarcoma (non-defective) Chicken Sarcoma

Avian Erythroblastosis Chicken Leukemia

Avian Myeloblastosis Chicken Leukemia

Avian Myelocytomatosis Chicken

Abelson Leukemia Mouse Leukemia

Harvey Sarcoma Rat Sarcoma

Kirsten Sarcoma Rat Sarcoma

Feline Sarcoma Cat Sarcoma

Simian Sarcoma Monkey Sarcoma

RNAOnc1

Examples of Oncogenic RNA VirusesAcute Transforming Viruses

What Genetic Information Makes Them Oncogenic?

Rous Sarcoma Chicken Sarcoma

Avian Erythroblastosis Chicken Leukemia

Avian Myeloblastosis Chicken Leukemia

Avian Myelocytomatosis Chicken

Abelson Leukemia Mouse Leukemia

Harvey Sarcoma Rat Sarcoma

Kirsten Sarcoma Rat Sarcoma

Feline Sarcoma Cat Sarcoma

Simian Sarcoma Monkey Sarcoma

Extra GenesrcerbmybmycablHa-rasKi-rasfmssisRNAOncG1

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Table 4.1 The Biology of Cancer (© Garland Science 2007). P. 100

Cell Site-of-action of Onc-Gene Products(from Scientific American)

sis

OncLocus

Site of Action of Onc-Gene Products

Nucleus• myc (N-myc, C-myc, L-

myc)• myb• fos• ski• jun• erb-AReceptor Tyr Kinases• erb-B (EGF Receptor)• erbB-2/neu (her-2/neu)• met• fms• kit• trkNon-receptor Tyr-Kinase• abl• src

Ser/Thr Kinases raf PKC (Protein Kinase C)GTP-Binding Proteins Ha-Ras N-Ras K-RasGrowth Factors sis int-2 hstOthers B-lym T-lym-1 bcl-1 (Cyclin D1) bcl-2

OncSite

Questions About V-Onc GenesAffecting the Biology of Cancer

• Where Does A Virus Get It From?• How Many Different V-Onc Genes Exist?• What Protein Does Each Code For?• What Do Those Proteins Do?• Where Do Those Proteins Do Their Thing?• Why Do They Cause Transformation?• How Do They Cause Transformation?• Do They Have a Normal function?• What Do They Tell Us About Neoplastic

Transformation Not Involving V-Onc Genes?OncQues1

Alternative Ways in Which Oncogenes Transform Cellular Gene Expression

• v-Onc Gene Insertion (Acutely Transforming Retrovirus)

• Activation of c-onc Genes (Sub-acutely transforming retroviruses and DNA viruses)

• Mutations in c-onc Genes

• Gene Rearrangements and Gene Fusions Involving c-Onc Genes

• Amplification of c-Onc GenesTransWay

Figure 4.2 (part 1 of 2) The Biology of Cancer (© Garland Science 2007) p. 96

Transfection of DNA from Transformed Cells into Normal Mouse Fibroblasts:

Figure 4.2 (part 2 of 2) The Biology of Cancer (© Garland Science 2007) p. 96

Determination of Transforming Ability of Transfected DNA Fragments

Figure 4.10 The Biology of Cancer (© Garland Science 2007)

Point Mutation Affecting Amino Acid 12 (Glycine) in H-RAS Gene Product in Human Bladder Cancer

Table 4.2 The Biology of Cancer (© Garland Science 2007) p. 106

In this picture, what is the purple stuff that is being administered to the normal mouse fibroblasts?You can identify it specifically or just generally.

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Figure 4.11b The Biology of Cancer (© Garland Science 2007) p. 107

Amplification of Endogenous c-Oncogene in Human Cancer:

N-Myc in Human Neuroblastoma.

Table 4.4 The Biology of Cancer (© Garland Science 2007) p. 111

Figure 4.15a The Biology of Cancer (© Garland Science 2007) p. 113

Translocation and Chromosome Fusion in the Activation of Endogeneous C-Oncogenes

Figure 4.15b The Biology of Cancer (© Garland Science 2007) p. 113

Fusion Oncoproteins in Human Malignancies; Bcr-Abl Fusion Proteins

C-Abl partCNL = Chronic neutrophilic leukemia

Table 4.5 The Biology of Cancer (© Garland Science 2007) p. 114

Questions About c-Onc GenesAffecting Prevention, Diagnosis, and

Treatment of Clinical Cancers• Can We Prevent Neoplastic Transformation

Based on Oncogene Effects?

• Can We Use Oncogene Expression for Diagnosis and Prognosis?

• Can We Tailor Existing Treatments Based on Oncogene Expression in a Patient?

• Can We Develop New Treatments Based on the Biochemistry of Oncogene Products?

OncQues2

c-Onc Genes Not Defined by V-Onc Gene Transfection from Virusesc-Onc Genes Perturbed by retrovirus integration

int-1 Mouse mammary tumor virusint-2 Mouse mammary tumor virusMLV1-1 Murine Leukemia Virus RatMLV1-2 Murine Leukemia Virus RatPim-1 Murine Leukemia Virus Rat

c-Onc Genes Detected by DNA TransfectionN-ras Neuroblastoma/leukemia/sarcomasB-lym B-cell lymphomamam Mammary carcinomasneu Neuroblastoma/glioblastoma

cOncFind