HC2 - Viruses, oncogenes & growth factors

Question 1

cancer as infectious disease

Answer 1

until late 19th century, Rous sacroma virus (RSV)

Question 2

virus

Answer 2

genetic material encapsulatedv

Question 3

viruses and cancer

Answer 3

viruses can transform infected cells in culture

Question 4

formation of foci

Answer 4

loss of contact inhibition

Question 5

permissive host

Answer 5

allow virus replication and are killed quickly

Question 6

non-permissive host

Answer 6

does not allow virus replication and causes transformation

Question 7

intergration of viral DNA into host genome

Answer 7

• exploit replication machinery

Question 8

HPV

Answer 8

99.7% of cervical carcinomas

Question 9

episomal virus

Answer 9

outside of host genome, hitchhike during mitosis

Question 10

retrovirus

Answer 10

reverse transcription to intergrate genetic material

Question 11

kidnapping and exploiting host genes

Answer 11

v-src and c-src

Question 12

existing normal genes

Answer 12

can be oncogenic

Question 13

a single gene

Answer 13

sufficient for oncogenic transformation

Question 14

virus vector

Answer 14

to deliver foreign DNA

Question 15

kidnapped genes

Answer 15

most are silent, over 30 proto-oncogenes

Question 16

induction of transformation

Answer 16

viral intergration next to proto-oncogene c-myc

Question 17

insertional mutagenesis (mechanism c-myc)

Answer 17

strong viral promotor forces overexpression of c-myc gene > uncontrolable cell proliferation

Question 18

viruses as carcinogenes

Answer 18

in 20% of cancers, HPV, Hep. B and C

Question 19

not all cancers caused by virusses

Answer 19

• cancers don’t propagrate between humans
• no outbreaks
• non-biological reagents can be carcinogenic > chemicals and radiation

Question 20

latent viruses

Answer 20

inactive proviruses can be reactivated by some chemicals > BrdU

Question 21

mutations as drivers for transformation

Answer 21

• transfection of foreign DNA to test oncogenic potential of genes
• oncogens act across species = evolutionary conserved

Question 22

cellular oncogenes

Answer 22

• often amplified in cancers
• multiple copies > increased protein production

Question 23

HER2 in 30% of breast cancers

Answer 23

correlated with poor patient prognosis

Question 24

tumor suppressor genes

Answer 24

counteract oncogenic transformation

Question 25

deletion or mutation tumor suppressor genes

Answer 25

releases breaks on cell proliferation

Question 26

proto-oncogenes

Answer 26

activated by genetic changes affecting protein expression or structure

Question 27

H-ras bladder carcinoma oncogene

Answer 27

identical in length to normal human DNA, somatic point mutation

Question 28

Burkitt's lymphoma

Answer 28

-chromosome translocation fusing regions of chromosomes 2, 14, 22 to a region of chromosome 8 - places myc proto-oncogene under control of transcriptional activators of immunoglobulines

Question 29

epidermal growth factor receptors (EGFR)

Answer 29

recognizes EGF and initiates intracellular signaling to promote growth

Question 30

trunction EGFR

Answer 30

- in some carcinomas and glioblastomas - lacks extracellular domain > sends growth-stimulatory signals even in absence of EGF

Question 31

hybrid proteins in chronic myelogenous leukemia (CML)

Answer 31

abl proto-oncogene kinase (ch. 9) fuses with bcr region (ch 22.) > deregulation of abl protein > emits strong growth-promoting signals

Question 32

MLL1 (ALL1) gene

Answer 32

- histone methylase participates in >50 fusions - affects chromatin structure and function

Question 33

different mechanisms for transformation

Answer 33

- changes in proto-oncogene expression level - changes in proto-oncogene structure - complex cellular control systems

Question 34

changes in proto-oncogene expression levels

Answer 34

- amplification - insertional mutagenesis = control by an external promotor - translocation = control by an active promotor of another gene

Question 35

changes in proto-oncogene structure

Answer 35

- truncation - hybrid protein - mutation

Question 36

complex cellular control systems

Answer 36

regulating levels of proteins posttranscriptionally

Question 37

coordination of cell behavior

Answer 37

growth-stimulatory signals from their environment

Question 38

cell membrane

Answer 38

barrier in cell transduction

Question 39

growth factors (GF)

Answer 39

- convey signals between cells in a tissue - dimerization and transphosphorylation

Question 40

cancer alters growth factor metabolism

Answer 40

- overexpression or change of receptors - enhanced autocrine signaling

Question 41

EGFR amplication glioblastomas

Answer 41

increased levels of receptors can trigger activation

Question 42

membrane-permeable ligands (small, hydrophobic)

Answer 42

- steroid sex hormones, retinoids, vitamin D - bind directly to nuclear recpetor