Biochemistry: Chapter 18 Molecular Biology Of Cancer

Front 1

What are normal genes called that promote proliferation or cell survival? What are they called when cancerous?

Back 1

1) proto-oncogenes
2) oncogenes

Front 2

How does a cell transform into a malignant cell?

Back 2

gain of function mutation in only 1 proto-oncogene

Front 3

What are the presenting signs of chronic myelogenous leukemia? What causes it? what results at the cellular level?

Back 3

1) pain and tenderness in skeleton, hemorrhagic signs like bruising, bleeding gums, and petechiae
2) myeloid cells contain abnormal Philadelphia chromosome
3) abnormal proliferation bone marrow cells, particularly large increase in nonlymphoid WBC

Front 4

What is a philadelphia gene? What is formed? What is abi?

Back 4

1) reciprocal tranlocation from chromosome 22 to 9 causing chronic myelogneous leukemia
2) a fusion protein is produced between Bcr from chrom 22 and Abi from chrom 9
3) Abi is a proto-oncogene that becomes oncogenic and activates ras pathway when the philadelphia gene is present

Front 5

Why do people leukemia tend to have various bleeding disorders?

Back 5

platelets are suppressed

Front 6

malignant neoplasms of epithelial origin are called?

Back 6

carcinomas

Front 7

are nevi tumors? what causes them?

Back 7

yes they are caused by a nest of melanocytes producing large amounts of melanin

Front 8

What are the 3 criteria to show that a cell is transformed?

Back 8

1) grows in absence of growth factors (cytokines)
2) does not adhere
3) form tumors when injected into mice

Front 9

oxygen and nitrogen atoms in DNA are targets of what? Give an example?

Back 9

1) electrophiles
2) dimethylnitrosamine

Front 10

What wave length of UV light is most associated with skin cancer?

Back 10

UVB 280-320nm

Front 11

What is believed to cause the high level of gastric cancer in the japonese?

Back 11

nitrosamine

Front 12

What is the MOA of nitrosamines?

Back 12

methylate guanine

Front 13

what oncogene is amplified in neuroblastomas?

Back 13

N-myc

Front 14

The oncogene erb-B2 is found in what cancer?

Back 14

breast carinomas

Front 15

loss of function occurs in what genes to produce cancer transformation?

Back 15

tumor-suppressor genes, repair enzymes, activators of apoptosis

Front 16

In addition to breast cancer what has brca1 been associated with?

Back 16

ovarian cancer

Front 17

In addition to breast cancer what has brca2 been associated with?

Back 17

pancreatic cancer

Front 18

Do men with brca1 genes develop breast cancer?

Back 18

no but men with brca2 do

Front 19

A woman expressing HER2 can be treated with what and what condition does she have?

Back 19

breast cancer, give her herceptin

Front 20

what is herceptin?

Back 20

monoclonal antibody

Front 21

how is the name of the oncogene represented? How is the protein product represented?

Back 21

1) italicized lower case letters like myc
2) upper case first letter like Myc

Front 22

What is the Ras protein? What activates it? Where do mutations in Ras occur to make it oncogenic?

Back 22

1) a monomeric G protein
2) growth factor
3) in the GTPase portion so that it never hydrolzes GTP and thus remains active

Front 23

What does Ras activate and what follows?

Back 23

Ras activates Raf (MAP kinase kinase kinase) which activates MEK (MAP kinase kinase) which activates MAP kinase which induces transcription of myc and fos which are protooncogenes

Front 24

What all does MAP kinase activate?

Back 24

myc, fos, AP-1

Front 25

When is C-myc tightly regulated in a normal cell but is increased in a tumor cell?

Back 25

S phase of cell cycle

Front 26

What activates AP-1 and what is it made of?

Back 26

1) MAP kinase activates
2) it is composed of jun and fos

Front 27

What is the first step a quiescent cell must undergo to proliferate? What is the subsequent phase?

Back 27

leave Go and enter G1 then go to S phase

Front 28

In what phase are the cells committed to divide?

Back 28

DNA replication begins in S phase so this is the point of no return

Front 29

What regulates the transition from one cell cycle to another?

Back 29

cyclin-CDK complexes

Front 30

CKIs do what to cell cycle progression?"

Back 30

slow it by inhibiting cyclin-CDK complexes

Front 31

In a quiescent cell what is Rb complexed with? What is the function of this other protein?

Back 31

1) E2F is complexed retinoblastoma gene product
2) E2F activates transcription factors to enter S phase when the Rb protein is phosphorylated and released

Front 32

what type of gene is Rb?

Back 32

tumor suppressor gene

Front 33

what can induce CKI?

Back 33

DNA damage so that CKI can prevent Rb from being phosphorylated

Front 34

10% of melanoma is associated with genetics. What are the genes?

Back 34

p16 and CDK4

Front 35

when do tumor-suppressor genes contribute to cancer? How is this different from proto-oncogenes?

Back 35

1) when both gene copies are inactivated
2) only have to inactivate one proto-oncogene

Front 36

what are the two best known tumor suppressor genes?

Back 36

rb and p53

Front 37

What is sporadic retinoblastoma?

Back 37

develop rb mutations in both gene copies

Front 38

p53 mutations lead to what?

Back 38

Li-Fraumeni syndrome which is characterized by multiple types of tumors

Front 39

50% of human tumors have what mutation?

Back 39

p53

Front 40

What is the function of p53?

Back 40

transcription factor that regulates cell cycle and apoptosis

Front 41

What is considered the gaurdian of the genome?

Back 41

p53

Front 42

What downstream effect does p53 have on rb?

Back 42

prevents phoporylation of rb and release of E2F

Front 43

What do cadherins do?

Back 43

glycoproteins that mediate Ca-dependent cell to cell adhesion

Front 44

intracellulary what are cadherins anchored to?

Back 44

catenins which bind actin

Front 45

Someone that inherits mutations in E cadherin is prone to what?

Back 45

diffuse type gastric cancer and metastisis in general

Front 46

What are the functions of catenins?

Back 46

1) anchor cadherin to actin
2) beta-catenin increases during the cell cycle when the inhibitor APC is low and allow beta-catenin to move to activate myc

Front 47

What is APC and what is its function?

Back 47

tumor suppressor gene that binds and inhibits beta-catenin which inhibits cell proliferation

Front 48

sporadic human colon cancer is associated with what?

Back 48

mutations in APC

Front 49

familial adenomatous polyposis is associated with what gene mutation?

Back 49

APC

Front 50

What is one of the phagocytic markers indicating apoptosis?

Back 50

phosphatidylserine

Front 51

What external signal can induce apoptosis? What internal signals can induce it?

Back 51

1) TNF
2) oxygen deprivation and radiation damage, impaired mitochondria

Front 52

Procaspases are cleaved to caspases. What are the different types of caspases?

Back 52

1) initiator caspases cleave procaspases
2) execution caspases which cleave other cellular proteins involved in cell integrity

Front 53

How are initiator caspases activated?

Back 53

1) death receptor pathway
2) mitochondrial integrity pathway

Front 54

What do execution caspases do?

Back 54

degrade kinases, actin, lamins,
DNA repair enzymes, etc

Front 55

What are the death receptors a subset of and what are they?

Back 55

1) TNF-1 receptors
2) Fas/CD95, TNF-R1, Death receptor 3

Front 56

What mitochondrial protein is needed to activate caspase 9?

Back 56

cytochrome c released from mitochondria during damage

Front 57

What are antiapoptic Bcl2 proteins? What is their function?

Back 57

1) Bcl-2, Bcl-x, Bcl-w
2) insert into mitochondria and interfere with channels that release cytochrome c and bind cytoplasmic Apaf which is needed to bind cytochrome c to initiate apoptosis