Lecture 23

Question 1

cancer

Answer 1

• a heterogenous group of disorders characterized by the prescience of cells that do not respond to the normal controls on cell division.
• cancer cells divide rapidly and continuously, creating tumors
• most, if not all, arise from defects in DNA

Question 2

tumors

Answer 2

masses of abnormal cells that crowed out normal cells and rob healthy tissues of nutrients.

Question 3

benign

Answer 3

if cells of the tumor remain localized

Question 4

malignant

Answer 4

if the cells invade other tissues

Question 5

metastasis

Answer 5

• when cells of an advanced tumor can separate and travel to distant sites in the body where they can create secondary tumors.
• genes that contribute to metastasis often encode components of the extracellular matrix and the cytoskeleton.
• others encode adhesion proteins which help hold cells together.

Question 6

Knudson’s theory

Answer 6

• proposed a model to explain the genetic basis of cancer based on his studies of retinoblastoma
• in cases where the disease affects just one eye, a single cell in one eye undergoes TWO successive mutations.
• Because the chance of these two mutations occurring in a single cell is remote, retinoblastoma is rare and typically develops only in one eye
• for the bilateral case, the child inherited one of the two mutations required for the cancer, and so every cell contains this initial mutation. All that is required is for one eye cell to undergo the second mutation. JUST ONE MORE MUTATION

Question 7

Knudson’s actual model of cancer

Answer 7

• Rarely, a single cell undergoes two somatic mutations resulting in a single tumor, for example, in one eye.
• a predisposed person inherits one mutation
• some cells undergo a single somatic mutation that produces cancer
• because only a single mutation is required to produce cancer, the likelihood of its occurring twice increases.
• multiple mutations are required to product cancerous cells.
• if one or more of the required mutations is inherited, fewer additional mutations are required to product cancer.

Question 8

clonal evolution

Answer 8

• the tumor cells acquire more mutations that allow them to become increasingly aggressive in their ability to propagate
• rate of clonal evolution depends on frequency of new mutation
• Defects in DNA repair and mutations that affect chromosomal segregation may contribute to the clonal evolution of tumors.

Question 9

The signals that regulate cell division fall into two basic types

Answer 9

• molecules that stimulate cell division

- molecules that inhibit cell division

Question 10

molecules that stimulate cell division

Answer 10

• a stimulatory gene can be made hyperactive or active at inappropriate times.
• mutations in stimulatory genes are usually dominant-acting; even the reduced amount of gene product by a single allele is sufficient to produce a stimulatory effect.

Question 11

oncogenes

Answer 11

mutated dominant-acting stimulatory genes that cause cancer

Question 12

molecules that inhibit cell division

Answer 12

• cell division may also be stimulated when inhibitory genes are made inactive
• mutated inhibitory genes generally have recessive effects; both copies must be mutated to remove all inhibition

Question 13

tumor-suppressor genes

Answer 13

• inhibitory genes in cancer that are recessive
• both alleles must be mutated before the inhibition of cell division is removed
• the failure of their function promoters cell proliferation
• defects in both copies of a tumor-suppressor gene are required to cause cancer

Question 14

proto-oncogenes

Answer 14

• they are responsible for normal cellular functions, but when mutated, they come oncogenes that contribute to the development of cancer.
• may become incorporated into a retroviral genome through recombination during infection
• within the retroviral genome, the proto-oncogene may become mutated to an oncogene that causes cancer when introduced back into a cell

Question 15

how a proto-oncogene is converted to an oncogene

Answer 15

• the gene is altered in the virus and the product produces cell proliferation
• the proto-oncogene may end up next to a viral promotor or enhancer that leads to overexpression
• a virus may insert into the gene, disrupting normal function.

Question 16

myc

Answer 16

transcription factor

Question 17

src

Answer 17

protein tyrosine kinase

Question 18

ras

Answer 18

GTP binding and GTPase

Question 19

RB

Answer 19

transcription factor

Question 20

p53

Answer 20

• transcription factor

- regulates apoptosis.

Question 21

origins of oncogenes

Answer 21

• src was isolated from retrovirus Rous sarcoma virus in 1970
• cancer-causing viruses were assumed to carry cancer-causing genes that were transmitted to the host

Question 22

retroviruses and oncogenes

Answer 22

• a retrovirus inserts its RNA into the cell, which undergoes reverse transcription and inserts into the host chromosome next to a proto-oncogene
• when the virus reproduces the proto-oncogene is incorporated into the virus
• in repeated rounds of viral infection and reproduction, the proto-oncogene becomes arranged or mutated or both producing an oncogene that is inserted back into the host chromosome.

Question 23

Signal transduction pathway

Answer 23

• whether cells pass through the cell cycle and continue to divide depends on a large number of internal and external signals
• external signals are initiated by hormones and growth factors. These molecules are often unable to pass through the cell membranes because of their size or charge; they exert their effects by binding to receptors on the cell surface, which triggers a series of intracellular reactions that then carry the message to the nucleus or other site with the cell.
• defects in signal transduction pathways are often associated with cancer.

Question 24

vascularization

Answer 24

• the growth of new blood vessels
• important to tumor progression
• supply oxygen and nutrients, which are essential to growth and survival of tumors

Question 25

angiogenesis

Answer 25

- another term for blood vessel formation - particularly those that supply oxygen and nutrients to cancerous tissues. - stimulated by growth factors and other proteins encoded by genes whose expression is carefully regulated in normal cells - in tumor cells, genes encoding these proteins are often overexpressed compared with normal cells.

Question 26

two processes control the rate at which mutations arise within a cell

Answer 26

- the rate at which errors arise in the course of replication - the efficiency with which errors are corrected

Question 27

defects in genes that encode components of DNA-repair systems

Answer 27

have been consistently linked with a number of cancers.

Question 28

Changes in chromosome number and structure

Answer 28

- most tumors contain cells with chromosome mutation, and some are associated with specific chromosome mutation - at least three types of chromosome rearrangements are associated with certain types of cancer - deletions, inversions, and translocations - chromosomal breakpoints may lie within tumor-suppressor genes, leading to disruption of function - translocations and inversions may bring together sequences from two different genes, generated a fused protein that stimulates some aspect of cancer - a potential cancer-causing genes may be moved to a new location, causing activation by different regulatory molecules.

Question 29

Viruses and cancer

Answer 29

- evidence that some viruses contribute to a few cancers in humans - retroviruses may cause cancer by mutating and rearranging host genes, converting proto-oncogenes into oncogenes - may alter expression of host genes.

Question 30

advanced tumors chromosome number and structure

Answer 30

- most advanced tumors contain a variety of chromosome abnormalities including extra chromosomes, missing chromosomes, and chromosome rearrangements.