Term
|
Definition
| Discovered a virus was causing cancer in chickens. (Rous Sarcoma Virus [RSV]). He did this by removing a piece of sarcoma, grinding it up with sand, and then passing it through a fine-pore filter. (this proved that the carcinogenic agent was very small) then injected the filtrate into a chicken. |
|
|
Term
|
Definition
| Normal chicken cells were placed in culture forming a monolayer (one cell thick). This is so the contact inhibition factors are activated. When one of these cells is infected with RSV, the contact inhibition is turned off and the cell begins to divide. |
|
|
Term
| Properties of transformed cells |
|
Definition
| Altered morphology, loss of contact inhibition, anchorage independent, immorality, reduced MGF requirement, density. |
|
|
Term
| How to determine whether or not the RSV was still physically present in transformed cells |
|
Definition
| A mutant of RSV was created that was capable of transforming chicken cells at 37, but not 41 (normal temperature chicken cells grow) Ts mutants would denature at 41. This proves that the RSV was still exerting influence on the chicken cells, because the Ts cells would revert back to normal morphology if the temperature was raised to 41. |
|
|
Term
|
Definition
| Cancer causing virus Human Papillomavirus, which is different than the RSV due to DNA rather than RNA genomes, and protein coats rather than lipid coats. |
|
|
Term
| Oncogenic viruses integrate their DNA into the host genome |
|
Definition
1 Chromosomal DNA can be separated from extrachromosomal SV40 viral molecules by a CsCl2 density gradient centrifugation
2 Following with a southern blot of chromosomal DNA isolated from SV-40 transformed hamster revealed presence of SV-40 DNA within host genome. |
|
|
Term
| How did RSV integrate its genome (comprised of RNA) into the genome of the human host (comrpised of DNA) |
|
Definition
1) The virus enters the cell and sheds it's envelope.
2) The caspid containing the ssRNA along with a reverse transcriptase enzyme remain inside the cell
3) The reverse transcriptase replicates the ssRNA into dsDNA, which can then be integrated into the host chromosome.
4) Acting normally, when the host cell replicates its DNA using RNA pol II, the viral ssRNA are translated and able to produce new viruses. |
|
|
Term
| Identification of the src oncogene, V-src. |
|
Definition
| [image]
[image]
1) Took wild type RSV RNA and used reverse transcriptase to make ssDNA copy of RNA.
2) Fragmented the DNA and hybridized to the transformation defective (td) (unable to transform the host cells into cancerous cells)
3) Everything was able to hybridize except for the src portion of the host DNA due to no complementary strand on td RNA (src gene responsible for transformation)
4) This remaining fragment was then radiolabeled, and therefore used a s ahybridization probe to detect src genes somewhere else. |
|
|
Term
|
Definition
| The transforming (sarcoma inducing) gene of Rous sarcoma virus. The protein product is pp60vsrc, a cytoplasmic protein with tyrosine-specific protein kinase activity (EC 2.7.10.2), that associates with the cytoplasmic face of the plasma membrane. |
|
|
Term
|
Definition
| Cellular src gene. When ensconsed with the cellular genome, the actions of src were compatible with normal cellular behavior. However, the v-src borne by the RSV genome acted as a potent oncogen, a gene capable of transforming a normal cell into a tumor cell. |
|
|
Term
|
Definition
| Two for assembly of virus materials, and one for production of reverse transcriptase, and one for v-src. |
|
|
Term
| Viral Oncogene Hypothesis |
|
Definition
| The host cell has the protooncogenic c-src in its genome.infection and integration of the ALV provirus dsDNA
1) transcription of the host DNA integrated with the viral DNA ultimately gives you the the hybrid ssRNA transcript, which is then repackaged into the progeny, which became what is now known as RSV[image] |
|
|
Term
|
Definition
| 1) A Phosphotase removes an inhibitory kinase.
2) Kinase adds activating phosphate to tyrosine group
3) An Nef protein is able to bind, thus activating the src-type protein kinase. [image] |
|
|
Term
|
Definition
| Some retroviruses are oncogenic because they insert into the genome adjacent to critical cellular genes.
ex. Analysis of B cell lymphomas revealed that a large number of the viral DNA was integrated into the chromosomal DNA segment carrying the c-myc proto-oncogene., the majority being within the first and second non-coding exons. (reading frame begins at second exon). This happens when integration occurs along any point of the genome, but when it happens at the src section. Due to the constituitively active ALV promotor, src production can go out of control
[image] |
|
|
Term
| Viruses Associated with Human Cancer |
|
Definition
HPV- Cervical cancer
HTLV - Leukemia
Epstein-Barr - Burkitts lymphoma
Hep B - Liver Cancer
Herpes 8 - Kaposi's Sarcoma. |
|
|
Term
| Mutations in Proto-oncogenes are associated with most human cancers |
|
Definition
| The protogenes that are affected usually include the proteins associated with mitogen receptor signal transduction pathways or proteins that control the cell cycle. |
|
|
