Chapter 18 (5)

The genes that normally regulate cell growth and division during the cell cycle include genes for growth factors, their receptors, and the intracellular molecules of signaling pathways. __in any of these lead to cancer.
__ viruses cause cancer in various animals, including humans.

The __, which causes __, has been linked to several types of cancer, notably __.
Research on tumor viruses led to the discovery of cancer-causing genes called __. Subsequently, close counterparts of these __were found in the genomes of humans and other animals.

The normal versions of the cellular genes, called __, code for proteins that stimulate normal cell growth and division.

How does a proto-oncogene become an oncogene?
· In general, an __arises from a genetic change that leads to an increase either in the amount of the __protein product or in the intrinsic activity of each protein molecule.

The genetic changes that convert __ to __ fall into three main categories.

What three categories do the genetic changes fall in?

Cancer cells are frequently found to contain chromosomes that have broken and rejoined incorrectly, translocating fragments from one chromosome to another.
If a translocated __ends up near an especially active promoter (or other element), its transcription may increase, making it an __.

The second main type of genetic change, __, increases the number of copies of the __in the cell.
The third type is a __either 1) in the promoter or an enhancer that controls a __, causing an increase in its expression, 2) in the coding sequence, changing the genes product to a protein that is more active or more resistant to degradation than the normal protein.

In addition to genes whose products normally promote cell division, cells contain genes whose normal products inhibit cell division, called__ because the proteins they encode help prevent uncontrolled cell growth.
Any mutation that decreases the normal activity of a __ may contribute to the onset of cancer, in effect stimulating growth through the absence of suppression.

The protein products of __ have various functions. Some __ normally repair damaged DNA, a function that prevents the cell from accumulating cancer-causing mutations. Other __ control the adhesion of cells to each other or to the extracellular matrix; proper cell anchorage is crucial in normal tissues- and often absent in cancers.

Still other __are components of cell-signaling pathways that inhibit the cell cycle.
The proteins encoded by many __ and __ are components of cell-signaling pathways.
Mutations in __ occur in about 30% of human cancers, and mutations in __ more than 50%.

The __protein, encoded by the __gene is a __ that relays a signal from a growth factor receptor on the plasma membrane to a cascade of protein kinases.
The cellular response at the end of the pathway is the synthesis of a protein that stimulates the __.

Normally, such a pathway will not operate unless triggered by the appropriate growth factor. But certain mutations in the __ gene can lead to production of a hyperactive __protein that triggers the kinase cascade even in the absence of growth factor, resulting in increased cell division.
In fact, hyperactive versions or excess amounts of any of the pathway’s components can have the same outcome: __.

In a pathway in which a signal leads to the synthesis of a protein that suppresses the cell cycle: the signal is __to the cell’s DNA.
· Operation of this signaling pathway blocks the cell cycle until the damage has been repaired. Otherwise, the damage might contribute to __formation by causing mutations or chromosomal abnormalities. Thus the genes for the components of the pathway act as __.

The p53 gene is a __. The protein it encodes is a specific transcription factor that promotes the synthesis of cell cycle- inhibiting proteins.
The p53 gene has been called the “__.” Once activated, the p53 functions as an activator for several genes.

Often p53 activates a gene called __, whose product halts the cell cycle by binding to __, allowing time for the cell to repair the DNA; the p53 protein can also turn on genes directly involved in DNA repair.

When DNA damage is irreparable, __ activators suicide genes, whose protein products cause cell death by __. Thus, in at least three ways, __ prevents a cell from passing on mutations due to DNA damage. If mutations do accumulate and the cell survives through many cell divisions cancer may ensue.

True or False:
More than one somatic mutation is generally needed to produce all the changes characteristic of a full-fledged cancer cell.
True False

__cancer: 1st sign is a __, a small, benign growth in the colon lining.
· The cells of the __look normal, although they divide unusually frequently. The tumor grows and may eventually become malignant, invading other tissues.
· The development of a __is paralleled by a gradual accumulation of mutations that convert__ to __ and knock out __.
· A ras oncogene and a mutated p53 tumor-suppressor gene are often involved.

About a half dozen changes must occur at the DNA level for a cell to become fully cancerous. These usually include the appearance of at least one active __ and the mutation or loss of several __.
Furthermore, since mutant __ are usually recessive, in most cases mutations must knock out both alleles in a cell’s genome to block tumor-suppression.

Most oncogenes behave as __alleles.
In many malignant tumors, the gene for __is activated.
Many mutations in colorectal cancer affect the tumor-suppressor gene __. It has multiple functions, including regulation of cell __and __.
__is the second most common type of cancer in the US.

Mutations in the __ or __gene are found in at least half of inherited breast cancers.
· A woman who inherits one mutant BRCA1 has __% probability of developing breast cancer before 50.
· Both BRCA1 and BRCA2 proteins are considered __ because their wild-type alleles protect against breast cancer and their mutant alleles are recessive.
· They both function in the cell’s DNA damage repair pathway.