Biochemistry Genes And Cancer Pgs. 32-46

Front 1

The Myc family of transcription factors is involved in ______________ ?

Back 1

cell growth and differentiation

Front 2

AP-1 proteins form (homodimers/heterodimers) which form (leucine zippers/alpha turn helices) and regulate (cell growth/cell motility)?

Back 2

heterodimers; leucine zippers; cell growth

Front 3

Name the two most commonly cited tumor suppressor genes.

Back 3

p53 and Rb

Front 4

T or F: Tumor suppressor genes up-regulate cell division.

Back 4

FALSE!!!

Front 5

p53 and Rb work by (binding transcription factors/binding DNA)

Back 5

binding DNA

Front 6

What is a mitogen?

Back 6

compounds which stimulate cell division

Front 7

T or F: DAG and TPA are mitogenic.

Back 7

True

Front 8

Fos and Myc can be stimulated by mitogens. What is the result of this stimulation?

Back 8

Cells are reprogrammed for cell growth and division.

Front 9

T or F: Cancer cells often rely on Fos and Myc in order to ramp up cell growth and division.

Back 9

True

Front 10

T or F: Antisense RNA technology can be used to inhibit cancers.

Back 10

True, these bind to RNA transcripts of oncogenes and inhibit them from being translated.

Front 11

Which oncogene is transcribed quicker after mitogenic stimulation, c-fos or c-myc?

Back 11

c-fos (peak at less than 2 hours), peak for c-myc is around 5 hours post-stimulation

Front 12

Why is myc so active in Burkitt's lymphoma?

Back 12

translocation

Front 13

Why does translocation often active proto-oncogenes to oncogenes?

Back 13

Loss of regulatory sites upstream of gene

Front 14

In Burkitt's lymphoma, c-myc oncogene is now regulated by what kind of regulator sites?

Back 14

Immunoglobulin regulatory sites which are very active = oncogene

Front 15

In Burkitt's lymphoma, myc loses an exon, which one?

Back 15

exon 1

Front 16

In Burkitt's lymphoma, what tell of cell grows uncontrollably?

Back 16

B-cell

Front 17

Estrogen receptors are also________

Back 17

transcription factors (like all steroid receptors)

Front 18

Estrogen receptors are (on the cell surface membrane/in the cytoplasm)

Back 18

in the cytoplasm

Front 19

What happens to estrogen receptors after binding their ligand?

Back 19

They dimerize and go the nucleus where they act as transcription factors (bind DNA via zinc fingers)

Front 20

As breast cancer advances, the cells will become (more/less) differentiated?

Back 20

less

Front 21

Is early or advanced breast cancer tamoxifen sensitive?

Back 21

early, advanced breast cancer is less responsive to tamoxifen

Front 22

What is tamoxifen?

Back 22

it binds estrogen receptors and deactivates them

Front 23

T or F: tamoxifen is only used after a breast tumor is found, never before.

Back 23

False, tamoxifen may be used a chemopreventative for those at high risk for breast cancer.

Front 24

Estrogen, in breasts, normally stimulates the development of _______

Back 24

breast epithelium

Front 25

Tamoxifen bind the hormone binding site on the estrogen receptor and _________

Back 25

switches the receptor to a different conformation (inactivation)

Front 26

T or F: tamoxifen structure highly resembles the structure of estrogen.

Back 26

False

Front 27

What other drug works as well as tamoxifen but does not promote uterine cancer?

Back 27

raloxifene

Front 28

Mutations in tumor suppressor genes are (recessive/dominant), while mutations in proto-oncogenes are (recessive/dominant)

Back 28

recessive;dominate - need 2 mutations for tumor suppressor genes to lose regulation, need only 1 mutation in proto-oncogenes to form an oncogene

Front 29

Main categories of tumor suppressor genes include: (3)

Back 29

1.transcription factors
2. cell adhesion molecules
3. signal transduction effectors

Front 30

Examples of tumor suppressor transcriptions factors include:

Back 30

p53, WT1 (Wilms) and RB1 (retinoblastoma)

Front 31

Examples of cell adhesion tumor suppressors:

Back 31

DCC

Front 32

Examples of signal transduction effector tumor suppressors:

Back 32

NF1-Ras GTPase

Front 33

Important tumor suppressor, whose mutation can result in breast cancer

Back 33

brca1

Front 34

Mutated forms of brca1 are found in the nucleus or cytoplasm?

Back 34

cytoplasm

Front 35

RB1 causes pediatric tumors in what structure?

Back 35

the eye

Front 36

RB1 protein binds to which transcription factor to inhibit its action?

Back 36

E2F

Front 37

E2F is responsible for:

Back 37

transition into the S-phase of the cell cycle

Front 38

In order for retinoblastoma to develop, is one mutated allele sufficient?

Back 38

No, both alleles must be mutated

Front 39

T or F: mutations in rb1 are responsible only for mutations of the eye?

Back 39

Fasle, they are responsible for pediatric cancers of the eye, but mutated forms of this gene are also present in a wide variety of adult cancers including breast, lung and pancreas

Front 40

Mutations in rb1 can inlcude (6):

Back 40

point, gene conversion, deletion, mitotic recombination, chromosomal loss and duplication, monosomy (chromosomal loss)

Front 41

T or F: Wilms tumors are pediatric lung tumors.

Back 41

False, they are pediatric kidney tumors

Front 42

The DNA binding domain of the Wilms tumor suppressor gene consists of four _______________.

Back 42

Cys 2 His 2 TFIIIA type zinc fingers

Front 43

When mutated, which of the 4 DNA binding domains is lost?

Back 43

number 3 - loss of norman DNA binding specificity

Front 44

What compound in tobacco smoke causes mutations in p53?

Back 44

benzopyrene

Front 45

Benzopyrene has what structure?

Back 45

polycyclic aromatic hydrocarbons

Front 46

T or F: Benzypyrene itself causes mutations.

Back 46

False, benzypyrene and other PAHs are not carcinogenic, but their oxidized detoxification products are

Front 47

benzypyrene is "detoxified" to _______

Back 47

diol-epoxide, which is actually highly reactive

Front 48

diol-epoxide causes what type of mutation?

Back 48

G-T transversion

Front 49

p53 mutations are (generally random/concentrated in hotspots)?

Back 49

concentrated in hotspots

Front 50

p53 binds DNA via ____________ which have 3 ______ residues and 1____ residue?

Back 50

zinc fingers; Cys; His

Front 51

Mutations in p53 will result in what consequence in the cell?

Back 51

Loss of p53 binding to DNA and loss of tumor suppression.

Front 52

Aggrecan is a protein in the _______

Back 52

ECM

Front 53

Aggrecanase function is:

Back 53

degradation of aggrecan

Front 54

Others proteins which degrade aggrecan are called_____________

Back 54

MMPs

Front 55

The proteinase domain of aggrecanase consists of __________?

Back 55

zinc coordinated by three histidine residues

Front 56

Cancer and arthritis are (dependent on/independent of) degradation of aggrecan and the ECM?

Back 56

dependent on

Front 57

Inhibitors of aggrecanase could possibly help in which two diseases?

Back 57

cancer and arthritis

Front 58

Elastase may be responsible for ____________?

Back 58

degeneration of lung tissue in emphysema

Front 59

How many zinc molecules are present in elastase

Back 59

2

Front 60

Inhibitors of MMPs have what kind of chelators?

Back 60

hydroxamic chelator