20.2 Oncogenes

Question 1

specific genes that can induce cell transformation (process of converting normal cells to tumor cells) → they can induce cancer

Answer 1

oncogenes

Question 2

studies of () led to identification of cellular oncogenes involved in developement of non-virus-induced cancers

Answer 2

retroviral oncogenes

Question 3

() transforms chicken embryo fibroblasts in culture and induces sarcomas

Answer 3

Rous sarcoma virus (RSV)

Question 4

RSV is closely related to () replicates in the same cells without inducing transformation → RSV contained specific genetic information for transformation

Answer 4

avian leukosis virus (ALV)

Question 5

studies of RSV mutants revealed a single gene called () responsible for RSV tumor induction

Answer 5

src

Question 6

many oncogenes encode components of signaling pathways that stimulate ()

Answer 6

cell proliferation (e.g. src, encoding Ras and Raf)

Question 7

studies involving the () found that even though a mouse was injected only with viral genes responsible for replication (i.e. no genes inducing transformation), it developed leukemia

Answer 7

Abelson leukemia virus

Question 8

the Abelson leukemia virus was found to induce leukemia due to the presence of an oncogene called ()

Answer 8

abl

Question 9

explain how viral oncogenes can have cellular origins

Answer 9

a host cell gene that can drive cell proliferation occasionally becomes incorperated into a viral genome → yields a highly oncogenic virus with an oncogene derived from the host cell

Question 10

normal genes from which retroviral oncogenes originated

Answer 10

proto-oncogenes

Question 11

oncogenes are () of the proto-oncogenes

Answer 11

abnormally expressed or mutated forms

Question 12

proto-oncogenes often encode proteins in the signaling pathways that () → these genes are triggered by growth factors

Answer 12

control normal cell proliferation (e.g. src, ras, raf)

Question 13

retroviral oncogenes differ from proto-oncogenes in the ff aspects:

Answer 13

1. transcription in viral oncogenes is controlled by viral promoters and enhancers
2. oncogenes often encode proteins that differ in structure and function from normal proteins
3. loss of regulatory domains generates in oncogenes proteins that function in an unregulated manner

Question 14

transcription in viral oncogenes is controlled by viral promoters and enhancers; this results in the oncogenes being ()

Answer 14

expressed at much higher levels than proto-oncogenes or in the wrong cells

Question 15

oncogenes such as Raf are expressed as fusion proteins with () at the amino terminus

Answer 15

viral sequences

Question 16

deletion of () leads to raf protein kinase hyperactivity → drives abnormal cell proliferation and then cell transformation

Answer 16

regulatory domain

Question 17

many oncogenes differ from proto-oncogenes by () → single amino acid substitutions in proteins, which then lead to unregulated protein activity

Answer 17

point mutations

Question 18

gene transfer experiments found evidence for involvement of cellular oncogenes in human tumors (not induced by viruses)

Answer 18

DNA from a human bladder carcinoma was found to induce transformation of mouse cells in culture → tumor contained an oncogene

Question 19

the first human oncogene identified was the homolog of the (1) of the (2)

Answer 19

1. rasH oncogene
2. Harvey sarcoma virus

Question 20

three members of the ras gene family () are the oncogenes most frequently encountered in human tumors

Answer 20

rasH, rasK, rasN

Question 21

mutations of ras oncogenes maintain the ras proteins in the ()

Answer 21

active GTP-bound conformation

Question 22

mutated ras proteins do not respond to GAP (GTPase-activating protein) → ()

Answer 22

GTP bound to Ras is not hydrolyzed to GDP to inactivate Ras

Question 23

many cancer cells have () → lead to generation of oncogenes

Answer 23

abnormal chromosome structures, including translocations, duplications, and deletions

Question 24

in Burkitt’s lymphoma, chromosome translocation inserts () oncogene into an (2), where it is expressed in an unregulated manner

Answer 24

1. c-myc
2. immunoglobulin locus

Question 25

translocation of abl proto-oncogene leads to production of a () → unregulated activity of Abl tyrosine kinase → cell transformation

Answer 25

bcr/abl fusion protein

Question 26

oncogenes can be activated by () → results in elevated expression

Answer 26

gene amplification

Question 27

amplification of the oncogene () (encodes RTK) is related to rapid growth of breast and ovarian tumors

Answer 27

erbB-2

Question 28

the main purpose of oncogene protein production is to (1), as well as to (2)

Answer 28

1. promote cell proliferation and survival 2. prevent programmed cell death

Question 29

functions of oncogene products include:

Answer 29

1. activation of the ERK pathway 2. transcriptional activation 3. increasing cell proliferation 4. inhibition of cell differentiation 5. promotion of cell survival

Question 30

all the components of ERK pathway () can serve as oncogene proteins

Answer 30

1. polypeptide growth factors 2. growth factor receptors 3. intracellular signaling proteins 4. transcription factors

Question 31

give an overview of how the receptor for platelet-derived growth factor (PDGFR) can act as an oncogenic product (due to chromosome translocation)

Answer 31

1. translocation results in PDGFRs with amino terminal sequences of the transcription factor Tel 2. PDGFR+Tel oncogene proteins have a dimerization domain that constitutively keeps the receptor active → even without PDGF stimulation, pathway is activated and cell continuously proliferates

Question 32

transcription of the () is induced by phosphorylation of Elk-1 by the ERK pathway

Answer 32

fos proto-oncogene

Question 33

explain how transcription of the fos proto-oncogene can lead to tumor formation

Answer 33

1. fos encodes for Fos, which dimerizes with Jun to form the AP-1 transcription factor 2. AP-1 transcription factor then activates transcription of cyclin D1 → promotes cell proliferation

Question 34

Fos dimerizes with Jun to form ()

Answer 34

AP-1 transcription factor

Question 35

() were identified as oncogenes in mouse breast cancers

Answer 35

Wnt proteins

Question 36

explain how Wnt proteins serve as oncogenes

Answer 36

1. Wnt signaling pathway triggers degradation of beta-catenin 2. mutations convert beta-catenin (downstream target of the Wnt pathway) to an oncogene called CTNNB1 3. CTNNB1 is more stabilized than beta-catenin → it is not degraded and can cause unregulated transcription of the c-myc oncogene as well as cycD1 (in coordination with the transcription factor Tcf)

Question 37

mutations convert beta-catenin (downstream target of the Wnt pathway) to an oncogene called ()

Answer 37

CTNNB1

Question 38

CTNNB1 is more stablized that beta-catenin → it is not degraded and can cause unregulated transcription of the c-myc oncogene as well as cycD1 in coordination with the transcription factor ()

Answer 38

Tcf

Question 39

gene encoding cycD1 (it is a proto-oncogene) can become an oncogene called () by chromosome translocation or gene amplification

Answer 39

CCND1

Question 40

catalytic partners of cycD1: () are also activated as oncogenes by point mutations, gene amplification, and chromosome translocation

Answer 40

Cdk4 and Cdk6

Question 41

mutated form of *thyroid hormone receptor* that can lead to maintaining leukemic cells in an actively proliferating state

Answer 41

ErbA

Question 42

mutated form of *retinoic acid receptor* that can lead to maintaining leukemic cells in an actively proliferating state due to blocking of cell differentiation

Answer 42

PML/RAR(alpha)

Question 43

acute promyelocytic leukemia can be treated with high doses of () → induces differentiation because effect of PML/RAR(alpha) oncogene is overridden

Answer 43

retinoic acid

Question 44

failure of cancer cells to () is a critical factor in tumor development

Answer 44

undergo programmed cell death

Question 45

PI 3-kinase and Akt act as oncogenes if they () → preventing cell death

Answer 45

constitutively keep the pathway active

Question 46

elevated expression of the antiapoptotic protein Bcl-2 also causes to serve as an oncogene by ()

Answer 46

blocking apoptosis