Neoplasia 2 Lecture

Question 1

Cancer

Answer 1

Genetic injury
- May be: acquired in somatic cells by environmental agents or inherited in the germ line
(tumors develop as clonal progeny of a single genetically damaged progenitor cell

Question 2

Heterogenicity

Answer 2

Take a tumor and it consists of different types of cells, some are evasive

Question 3

Exposure to carcinogens

Answer 3

Radiation, heavy metals, chemicals, retroviruses, environmental factors or genetic defects

Question 4

Retrovirus?

Answer 4

RNA virus

• MMTV (mouse mammary tumor virus
• – mimics DNA of the host so it is incorporated (taken up and made into DNA in order to be able to be incorporated into the host)

Question 5

Four classes of genes

Answer 5

Growth promoting protoncogens
Growth inhibiting genes
Genes that regulate apoptosis
Genes that regulate DNA repair
-- All play togehter

Question 6

Normal cell undergoes some type of damage

Answer 6

Repair mechanisms comes in

• Once the DNA can be fixed it can go back to being a normal cell
• BUT if that fails, the mutation will be inherited
• – In somatic cells, they form a tumor because it is growth-promoting genes, inactivating tumor suppressor genes or apoptotics genes (blocking apoptosis – not removed leading to unregulated cell proliferation)

Question 7

Clonal expansion

Answer 7

Angiogenesis: new blood supply, supplying oxygen so it can use ATP

Question 8

Tumors are able to stay how?

Answer 8

Develop and escape system in order to stay

• • Additional mutations –> tumor progression
• • Invade and metatasize

Question 9

Define oncogenes

Answer 9

Genes who products are associated with neoplastic transformations (help cancer grow)

Question 10

Define protoncogenes

Answer 10

Normal cellular genes that affect growth and differentiation

– Become oncogenes when mutated

Question 11

v-onc

Answer 11

Transduction into retroviruses

Changes in situ that affect their expression, function, or both, thereby converting them into c-onc

Question 12

DNA contains transforming sequences (c-onc)

Answer 12

transfected fibroblasts acquire the growth characteristics of neoplastic cells

Question 13

How is a stimuli transmitted in the cell?

Answer 13

External stimuli, ligand

• When bound it sends a signal
• At the membrane there is some type of activation
• Signal transduces cellular mediators
• Activation leads to nuclear activation of factors in the nucleus
• Activation of gene activation (cell proliferation, division, inhibition)

Question 14

Different types of receptors?

Answer 14

Intrinsic kinase activity: kinase in the domain
Without intrinsic kinase activity
GPCRs: G proteins for activation

Question 15

Platelet-derived growth factor

Answer 15

Help cells related to the migration (blood cells: growth, proliferation)
- Over expression: uncontrolled cell growth

Question 16

TUmors that produce growth factors:

Answer 16

Responsive to the growth-promoting effects of the secreted growth factors and hence subject to autocrine stimulation

Question 17

Growth Factor Receptors

Answer 17

(receptor tyrosine kinase)

- Mutations can lead to constitutive activation without binding to their ligands (uncontrolled cell growth)

Question 18

Guanosine Triphosphate Binding Proteins (RAS family)

Answer 18

Normal flip back and forth between an active (GTP bound) and an inactive (GDP-bound) form

• Mediated by intrinisic GTPase activity, augmented by GTPase-activating proteins (GAPs)
• MutantsRAS bind GAP but their GTPase activity fails to be augmented and they are trapped in the signal transmitting from
• 10-20% of all human tumors carry mutant ras proteins

Question 19

c-ABL gene

Answer 19

Normal form exerts a regulated tyrosine-kinase activity
- Luekemia, translocation of c-ABL and its fusion to the BCR gene produce a hybrid gene with potent, unregulated tyrosine-kinase activity

Question 20

Nuclear Transcription Proteins

Answer 20

Products of MYC, JUN, FOS, MYB

• Highly regulated during proliferation of normal cells
• Regulate transcription of growth-related genes
• Staying on leads to tumor or continuous cell proliferation

Question 21

MHC expressions

Answer 21

Occurs in Burkitt’s lymphoma, neuroblastomas, and small cell cancer of the lung

Question 22

Cyclins and cyclin-dependent kinases

Answer 22

Regulate the progression of cells through the cell cycle

• D-type cyclins facilitate the trasition from G1 to S phase via CDK4 and CDK6 –> phosphorylate the retinoblastoma protien, releases E3F transcription factors (allows synthesis of S phase genes)
• – Inhibiting of CDKs via CDK inhibitors inhibit cell division (helps in DNA repair times)

Question 23

Over expression of what is common in cancers

Answer 23

Cyclin D and CDK4

Question 24

Oncogenes

Answer 24

Cancer may arise due to failure to repair the damage DNA

Question 25

Protoncogenes may be converted to oncogenes via?

Answer 25

Point mutations
Chromosomal rearrangements
Gene amplification

Question 26

Point Mutations

Answer 26

~15% of all human tumors carry mutated H-RAS or K-RAS oncogenes

• – RAS losses the ability of GTPase –> stays in active state
• Exposure to chemicals, etc

Question 27

Chromosomal Rearrangements activate protooncogenes how?

Answer 27

Placement of the genes next to strong promoter/enhancer elements (c-MYC next to heavy chain gene)
Fusion of the gene with new genetic sequences (c-ABL gene with BCR)

Question 28

Gene amplification

Answer 28

Reduplication of protooncogenes can lead to increased expression or activity

• Amp of c-ERB B2 in breast cancers
• Trisomy