Chapter 20 Flash Cards

20.1 Progression of cells through the cell cycle is tightly
regulated, and cancerous cells fail to respond to signals
that normally regulate cellular proliferation.
a. Which stages of the cell cycle are subject to regulation?
b. What types of proteins reg

a.)The cell cycle is regulated at cell cycle checkpoints that occur between G1 and S, G2 and M, and during M just before the separation of chromatids.
b.)The cyclins and cyclin-dependent kinases (Cdks) regulate progression through the cell cycle. At each

20.2 Explain why HIV-1, the causative agent of AIDS, is
considered a nononcogenic retrovirus, even though numerous
types of cancers are frequently seen in patients
with AIDS.

HIV-1 is a retrovirus that kills cell of the immune system. This leads to the susceptibility to certain types of cancer.

20.3 Distinguish between a transducing retrovirus and a
nontransducing retrovirus.

Retroviruses are viruses that have two copies of an RNA genome within a protein core surrounded by a membrane envelope. Transducing retroviruses carry an oncogene from a host cell, nontransducting retroviruses do not. Transducting retroviruses may be capa

20.4 Cellular proto-oncogenes and viral oncogenes are
related in sequence, but they are not identical. What is
the fundamental difference between the two?

Cellular proto oncogenes are important in regulating cell division and differentiation. Viral oncogenes are mutated, abnormally expressed forms of protoncogenes that cause neoplastic growth. Viral oncogenes lack introns and are often fused to viral genes.

*20.5 An autopsy of a cat that died from feline sarcoma revealed neoplastic cells in the muscle and bone marrow but not in the brain, liver, or kidneys. To gather evidence for the hypothesis that the virus FeSV contributed to
the cancer, Southern blot ana

If FeSV contrtibuted to feline sarcoma, FeSV should be found in the neoplastic tissues (muscle and bone marrow). The Southern blot provides this evidence. The fes proto oncogene is found normally in a cat, while the FeSV fes oncogenese is found in a retro

*20.6 The sequences of proto-oncogenes are highly conserved
among a large number of animal species. Based on
this fact, what hypothesis can you make about the functions
of the proto-oncogenes?

This suggests that they function in normal, essential, conserved cellular processes. Given the relationship between oncogenes and proto oncogenes, it also suggests that cancer occurs when these processes are not correctly regulated.

*20.7 Proto-oncogenes produce a diverse set of gene products.
a. What types of gene products are made by protooncogenes?
Do these gene products share any features?
b. Which of the following mutations might result in an
oncogene?
i. a deletion of the entir

a.Proto oncogenes encode for growth factors, receptor and nonreceptor protein kinases, receptrors lacking protein kinase activity, membrance associated GTP-binding proteins, cytoplasmic regularots involved in intracellular signaling, and nuclear transcrip

20.8 Explain the likely mechanism underlying the formation of an oncogene in each of the following
mutations:
a. a mutation in the promoter for platelet-derived growth factor that leads to an increase in the efficiency of transcription initiation
b. a mut

increased transciption of the mRNA will lead to increased levels of the the growth factor which will stimulate fibroblast growth and division.
Constitutive activation of a nonreceptor tyrosine kinase could lead to abberant, unregulated phosphorylation and

20.9 Describe a pathway leading to altered nuclear transcription
following the binding of a growth factor to a surface-membrane-bound receptor. How can mutations in genes involved in this pathway result in oncogenes?

See text figure 20.6 for illustration (pg 587). The binding of EGF to its surface membrane bound receptor stimulates a signaling cascade that leads to transcriptional activation of cell cycle specific targer genes.
1. EGF binding stimulates autophosphoryl

*20.10 What are the three main ways in which a protooncogene
can be changed into an oncogene?

A proto oncogene can be changed into an oncogene if there is an increase in the activity of its gene product or an increase in gene expression that leads to an increased amount of gene product. This can result from point mutation, deletion, or gene amplif

20.11 List two ways in which cancer can be induced by a
retrovirus.

one mechanism is by which a transducing retrovirus causes cancer is for the viral oncogene it carries is expressed under the control of retroviral promoters. A second mechanism involves insertional mutagenesis that results when the proviral DNA of a retro

*20.12 After a retrovirus that does not carry an oncogene infects a particular cell, northern blots indicate that the amount of mRNAs transcribed from a particular
proto-oncogene became elevated approximately thirteenfold
compared with uninfected control

The proviral DNA has integrated near the proto oncogene and the expression of the proto oncogene has come under the control of promoter and enhancer sequences in the retroviral LTR. This could be tested by performing a whole genone Southern blot analysis

*20.13 In what ways is the mechanism of cell transformation
by transducing retroviruses fundamentally different
from transformation by DNA tumor viruses? Even though the mechanisms are different, how are both able to cause neoplastic growth?

Tumor growth induced by transforming retrovirsus results either from the activity of a single viral oncogene, or from the activation of a proto oncogene caused by the nearby integration of the proviral DNA. The oncogene can cause abnormal cellular prolife

*20.14 You have a culture of normal cells and a culture
of cells dividing uncontrollably (isolated from a tumor).
Experimentally, how might you determine whether uncontrolled
growth was the result of an oncogene or a mutated
pair of tumor suppressor allel

Fuse cells from the 2 cell lines and then test the resultant hybrids for their ability to form tumors. If the uncontrolled growth of the tumor cell line as caused by a mutated pair of tumor suppressor allelels, the normal alleles present in the normal cel

*20.15 What is the difference between a hereditary cancer
and a sporadic cancer?

Hereditary cancer is associated with the inheritance of a germ-line mutation; sporadic cancer is not. For some cancers, both hereditary and sporadic forms exist with the hereditary being less frequent.

20.16 Why are mutations in tumor suppressors, such as mutations in RB and TP53, said to cause recessive disorders when they appear to be dominant in pedigrees?

Mutations in tumor suppressor genes such as RB and TP53 are recessive because the cancer develops only if both alleles are mutant. The presence of a normal allele in a heterozygote serves to suppress tumor formation (normal allele is dominant). The disord

20.17 Individuals with hereditary retinoblastoma are heterozygous for a mutation in the RB gene; however, their cancerous cells often have two identically mutated
RB alleles. Describe three different mechanisms by which the normal RB allele can be lost. I

A second mutational hit at the RB locus would result in a loss of heterozygosity and produce a cell that is rb/rb . Chromosome nondisjunction during mitosis could also produce a cell with 2 identical alleles. A third mechanism that would lead to the loss

*20.18 Although there has been a substantial increase in our understanding of the genetic basis for cancer, the vast majority of cases of many types of cancer are not hereditary.
a. How might studying a familial form of a cancer provide
insight into a sim

a.)Studies of hereditary forms of cancer have led to insights into the fundamental cellular processes affected by cancer.
b.)A genetic predisposition to cancer refers to the presence of an inherited mutation that can lead to cancer. Although there is a su

*20.19 Suppose a germ-line mutation leads to a zygote
having an constitutively activated oncogene. What consequences
will this mutation have for zygotic development? Based on your answer, why are most inherited
forms of cancer associated with loss-of-func

A mutation causing the constituative activation of an oncogene is a gain of function mutation. It would lead to unregulated cell proliferation anf the failure of cells to undergo terminal differentiation. It is likely that this mutation in a heterozygous

20.20 Explain how progression through the cell cycle is regulated by the phosphorylation of the retinoblastoma protein pRB. What phenotypes might you expect in cells where
a. pRB was phosphorylated constitutively?
b. pRB was never phosphorylated?
c. a sev

a.)It would never bind to E2F, there would be no inhibition of cell cycle progression at G1/S and neoplastic growth would occur.
b.) pRB was never phosphorylated
Cells would be stalled in the G0 phase and eventually undergo apoptosis
c.) a severly truncat

20.21 Mutations in the TP53 gene appear to be a major factor in the development of human cancer.
a. Discuss the normal cellular functions of the TP53
gene product and how alterations in these functions can lead to cancer.
b. Explain how mutations at both

a.)The TP53 gene produces the transcription factor p 53. P53 has cellular roles in the repair of DNA damage, in protecting against oncogenes, and in apoptosis. The p53 protein is regulated by phosphorylation and by interactions with another phosphoprotein

20.22 The p53 protein can influence multiple pathways
involved in tumor formation.
a. Explain how the functions of p53 are regulated by phosphorylation.
b. Through what pathway does the phosphorylation of p53 influence phosphorylation of pRB to control ce

a.) In a normal cell neither p53 nor Mdm2 is phosphorylated. They bind together and Mdm2 stimulates degradation of p53 so that the amount of p53 is kept low in normal cells. When DNA damage occurs, both p53 and mdm2 are phosphorylated so that their intera

20.23 What roles do non-protein-coding RNAs have in cell transformation and carcinogenesis? What is the molecular basis of the action of these RNAs?

MiRNA are short, single stranded, noncoding RNA regulatory molecules that can silence genes after transcription by RNA interference. MiRNAs normally serve regulatory roles in many biological processes including cell proliferation, differentiation, apoptos

20.24 As illustrated in Figure 20.6 (p. 587), Ras is a membrane-associated G-protein with a GTPase activity that is important for the transcriptional activation of
genes that control the cell cycle. The K-Ras G12D mutation changes its twelfth amino acid f

MiRNAs function to silence genes post trasncriptionally by RNA interference. The miRNA sequence is assembeled into a miRISC complex and the miRNA binds complementary of near complementary sequences in the 3' untranslated regions of target mRNAs. This inhi

*20.25 The proto-oncogene c-myc encodes a transcriptionfactor that regulates cell proliferation, growth, andapoptosis. As discussed in the text, mutations that abnormally
activate c-myc expression lead to the formation of amyc oncogene. The proto-oncogene

a.)See book for diagram
b.)E2F1 and c-myc are proto oncogenes since they normally function to promote cell cycle progression. The two miRNAs that negatively regulate E2F1 are tumor suppressor genes since they normally function to inhibit cell cycle progre

*20.26 What is apoptosis? Why is the cell death associated with apoptosis desirable, and how is it regulated?

Programmed cell death. Cells that are targeted for apoptosis are those that have high levels of DNA damage. Apoptosis is regulated by p53 among other proteins. In cells that have a large amount of DNA damage p53 accumulates and functions as a transcriptio

*20.27 Mutations in mutator genes lead to an increasedrisk of cancer even though the normal alleles of thesegenes are neither proto-oncogenes nor tumor suppressor
genes. How do these mutations lead to an increased risk
of cancer?

The products of normal alleles of mutator genes function in DNA repair processes. In the absence of a functional allele at such a gene, there is a dramatic increase in the accumulation of mutations. Some mutations will be at proto oncogenes and lead to fo

20.28 Two alternative hypotheses have been proposed to explain the functions of BRCA1 and BRCA2. One hypothesis proposes that these are tumor suppressor genes,
while the other proposes that these are mutator genes.
a. Distinguish between a tumor suppresso

a.) Tumor suppressor gene- suppresses uncontrolled proliferation that is characteristic of cancer cells
Mutator gene- any gene that when mutant increases the spontaneous mutation frequencies of other genes
b.) Both have been proposed to function in homolo

20.29 Telomerase activity is not normally present in differentiated
cells, but is almost always present in cancerous cells. Explain whether telomerase activity alone can lead
to cancer. If it cannot, why is it present in most cancerous cells, and what wou

Telomerase activity alone does not lead to cancer. The presence of telomerase enables cancer cells to maintain telomere length. Long telomeres=chromosome stability and enable cells to proliferate indefinitely. Cancerous cells without active telomeres are

20.30 Explain whether the following statement is correct,
and why: "Even though metastatic cancer cells are clonal descendants of a somatic cell that became cancerous, they are genetically distinct from that cell.

The metastic cancer cells that are clonal descendants of a somatic cell are genetically distinct from that somatic cell because they have accumulated additional mutations during the development of cancer.

*20.31 Material that has been biopsied from tumors is useful for discerning both the type of tumor and the stage to which a tumor has progressed. It has been known for a long time that biopsied tissues with more differentiated cellular phenotypes are asso

Tumors result from multi mutational steps that involve activation of oncogenes and the inactivation of tumor suppressor genes. The analysis of a hereditary form of colorectal cancer has shown that the more differentiated cells found in benign early stage

*20.32 Some tumor types have been very frequently associated
with specific chromosomal translocations. In some cases, these translocations are found as the only cytogenetic abnormality. In each case examined to date, the chromosome breaks that occur resul

a.) Might mean that they are a key event in tumor formation. It does not necessarily mean they are the primary cause of the tumor.
b.) A chimeric fusion protein may have different functional properties than either of the two proteins from which it derives

*20.33 What mechanisms ensure that cells with heavily damaged DNA are unable to replicate?

To go from G1 to S one or more G1 cyclins bind to the cyclin dependent kinase CDC28/cdc2 and activate it. Cyclin dependentkinase then phosphorylates key proteins that are needed to go into S. The p53 protein acts as a transcription factor to activate WAF1

*20.34 Distinguish between direct-acting carcinogens, procarcinogens, and ultimate carcinogens in the induction
of cancer.

Direct-acting carcinogens are chemicals that bind to DNA and act as mutagens. Procarcinogens are chemicals that must be converted by normal cellular enzymes to become active carcinogens. These products are called ulitimate carcinogens.

20.35 What sources of radiation exist, and how does radiation
induce cancer?

Sources of radiation include the sun, cell phones, radioactive radon gas, electriv power lines, x rays, and some household appliances. Radiation increases the amount of DNA damage in cells. If this damage is not repaired or is repaired incorrectly mutatio