Ch 4: Cellular Oncogenes

What is the main theory of how most human cancers arise, as proposed by researchers in the mid-1970s?

The mutation by carcinogens of normal growth-controlling genes, converting them into oncogenes.

What novel experimental strategy was devised to verify that transformed cells carry mutated genes functioning as oncogenes?

DNA from chemically transformed cells was introduced into normal cells in a procedure called transfection.

What evidence indicated that oncogenes could arise in cell genomes independently of viral infections?

Cultures of NIH 3T3 cells transfected with DNA from chemically transformed mouse cells yielded transformants that were anchorage-independent and tumorigenic.

What did experiments using human tumor donor cells transfected into murine cells demonstrate?

Oncogenes could act across species and tissue boundaries to induce cell transformation.

What was discovered about the source of oncogenes detected in human tumor cells and those of transforming retroviruses?

They both derive from a group of preexisting normal cellular genes.

What implication does increased copy number of proto-oncogenes in tumor cell genomes have?

It suggests that gene amplification results in increased levels of protein products that favor cancer cell proliferation.

What established a new mechanism for oncogene activation in the absence of viruses?

The discovery of a point mutation in the H-ras gene yielding a structurally altered protein.

What are the two activation mechanisms that might collaborate to create an active oncogene?

Regulatory and structural mechanisms.

Where was the myc oncogene initially discovered?

In the genome of an avian retrovirus.

What are the three alternative mechanisms through which the myc oncogene is activated in cancer cells?

Provirus integration, gene amplification, and chromosomal translocation.

What does gene amplification result from?

Preferential replication of a segment (an amplicon) of chromosomal DNA.

What is translocation in the context of cancer genetics?

The fusion of a region from one chromosome to a non-homologous chromosome.

What effect can translocation have on gene expression?

It can place a gene under the control of a foreign transcriptional promoter and lead to its over-expression.

What can result from the fusion of two protein-coding sequences due to translocation?

A hybrid protein that functions differently than the two normal proteins.

How can changes in protein structure lead to oncogene activation?

For example, truncation of the EGF receptor leads to continual growth-promoting signals.