Fabian cancer biology slide 1-40

Question 1

What causes cancers in modern day?
What happens to cancer cells in cell division?

Answer 1

-viruses, chemical carcinogens and radiation
-the cells with damaged DNA do not stop, cancer cells divide out of control

Question 2

What are the 6 key hallmarks of cancer?

Answer 2

-sustaining proliferative signaling
-evading growth suppressors
-enabling replicative immortaility
-activating invasion and metastasis
-genome instability and mutation
-resisting cell death

Question 3

How can you transmit tumor?
What happened in the sarcoma virus filtering process?

Answer 3

-can transmit tumor fragment through implantation
-filtered tumor homogenate was infectious and led to new tumors

Question 4

What is rous sarcoma virus?
What was special about the experiment in terms of the filtrate?

Answer 4

-it is a virus that is a carcinogenic agent
-filtrate was able to transmit the cancer just as well as injecting a small piece of tumor since it was infectious

Question 5

What are the first 3 steps in cellular transformation?

Answer 5

-1.immortilization (transformed cells are immortilized but not all immortilized cells are transformed
2. altered morphology (round shape)
3. loss of contact inhibition (ability to grow over one another, since normally cells are nice and spread out)

Question 6

What are the last 4 steps in cellular transformation?
-What type of growth is there, increased transport of, and what can form?

Answer 6

4.Anchorage-independent growth (growing without attachment to solid substrate)
5.reduced requirement for growth factors
6.increased transport of glucose
7. tumorgenicity (can form tumors)

Question 7

When would anchorage indepdendent growth not occur?
What do we use to see the increasde transport of glucose/

Answer 7

-when the cell is immortilized but not transfomed, the cell will no grow without attachment to solid substrate
-we use PET (positron emission tomography) to visualize tumors in the body that have concentrated large amounts of glucose

Question 8

What can HPV infect?
What is RSV (rous sarcoma virus)?
What is RSV enzyme use to transcribe?

Answer 8

-can infect cervical epitelial cells which can lead to cervical carcinoma
-it is a retrovirus that uses encoded enzyme (reverse transcriptase) to reverse transcribe their RNA genomes into complementary DNA(cDNA) which can then integrate into cellular genomes.

Question 9

What does RSV contain compared to other retrovirus?
Why did they name it src, based on what?
Why is src critical?

Answer 9

RSV contains anadditional genecompared to other avian retroviruses….
* Named it src based on the fact that it has arole in triggering
formation of sarcomas.
-to allow RSV to transform cells

Question 10

What was found in both rsv infectd and uninfected cells?
What did this find mean?

Answer 10

-found src DNA sequence in both RSV-infected and uninfected cell
-that cellular genes play a role in cancer

Question 11

How does ALV integrate, what does it transcribed to?

Answer 11

ALV pro-viral DNA (red) integrates by chance next to c-src and then gets transcribed and packaged into new viral particle (RSV

Question 12

What is c-src vs v-src?

Answer 12

-c-src= cellular src gene that is proto oncogene
v-src (viral src gene)=oncogene

Question 13

What are examples of 6 oncogenes that are present in non viral induced cancer?

Answer 13

-abl (non receptor TK)
-erb2 (receptor TK)
-raf (ser/thr kinase)
-H-ras (small g protein)
-K-ras (small g protein)
-myc (transcription factor)

Question 14

What is a kinase?
What is a tyrosine kinase?
What can src also do?

Answer 14

Kinase: an enzyme that removes high-energy phosphate group from ATP and transfers it to a suitable protein substrate.
-phosphorylates specific Tyrosine amino acids in substrates
-Src can also phosphorylate itself (autophosphorylation)

Question 15

What do kinases modify? by doing what?

Answer 15

-Kinases generally phosphorylate and thereby modify the functional state of substrate proteins.

Question 16

What do Akt/PKB kinase influence?
What are many kinases?

Answer 16

Akt/PKB kinase influences multiple biological processes by phosphorylating a number of downstream substrates.
* Many (but not all) oncogenes are kinases.

Question 17

How do you get cell signal from outside of the cell to inside?

Answer 17

-there is a cascade of signaling events that occur with kinases from an external signal that can lead to gene transcription

Question 18

What is an oncogene vs proto-oncogene?

Answer 18

-Oncogene: A gene that increases the selective growth advantage of the cell in which it resides.
-Proto-oncogene: A normal gene that can become an oncogene as a result of mutations or increased expression

Question 19

WHat is a tumor suppressor?

Answer 19

A gene that when inactivated or lost leads to an increase in the selective growth advantage of the cell in which it resides.
-it typically acts to slow cell down

Question 20

What is the comparison when you convert from an proto oncogene to an oncogene?
What about when a tumor supressor gene becomes inactivated?

Answer 20

-too much gas
-no brake

Question 21

How do you test that carcinogens function as mutagens that induce cancer by turning proto oncogene to oncogene?

Answer 21

-To test this, they introduced DNA of cancer cells into normal recipient cells by a process called transfection.

Question 22

what do you start with for transfection experiments?
What did we use for this?
What else do we treat the mice with for transfection

Answer 22

-start with immortilized fibroblasts that have not been transformed
-Used NIH 3T3 cells, immortalized fibroblasts that are great at taking up DNA.
* Treated mouse cell line with 3-methylchloranthrene (3-MC), a potent carcinogen that is a component of coal tars

Question 23

What are the 4 ways that you can turn on a proto oncogene into an oncogene/

Answer 23

-amplification
-insertion/deletion (indel)
-translocation
-point mutation

Question 24

What is amplification and an indel?

Answer 24

Amplification: A genetic alteration producing a large number of copies of a small segment of the genome.
Insertion/deletion (Indel): insertion or deletion of a few nucleotides.

Question 25

What is a translocation and point mutation?

Answer 25

translocation: A specific type of rearrangement where regions of two nonhomologous chromosomes are joined (e.g. Philadelphia chromosome).
Point Mutations: single-nucleotide substitutions (e.g. A to G) (changes in amino acid

Question 26

What is a driver mutation vs a passenger mutation?

Answer 26

Driver mutation: a mutation that directly or indirectly confers a selective growth advantage to a cell.
Passenger mutation: a mutation that does not confer a selective growth advantage (“along for the ride”)

Question 27

What does oncogene and tumor suppressor inactivation increase

Answer 27

-increases the growth advantage (driver mutation)

Question 28

What are the different cancers that can cause a higher mutation rate?

Answer 28

Question 29

What does BCR-abl do?

Answer 29

it is a cellular oncogene

Question 30

What is karyotyping?
what does colchicine do?
What is cytogenetics?

Answer 30

process of pairing and orderinng a cell’s chromosomes
-colchicine prevents MT polarization
-Cytogenetics: The study of inheritance in relation to the structure and function of chromosomes

Question 31

What occurs in a philedelphia chromsome?
What gets connected to each other?

Answer 31

The Philadelphia chromosome: a translocation between
chromosomes 9 and 22
-bcr gets connected to abl which causes abl to lose its regulation so it is always firing

Question 32

What does bcr-abl translocation lead to?

Answer 32

BCR-Abl: translocation leads to a ‘new’ gene in CML (Chronic myeloid leukemia)

Question 33

What is abl and bcr
What does their fusion lead to?

Answer 33

Abl: tyrosine kinase (proto-oncogene)
* Bcr (breakpoint cluster region):
Fusion leads to Abl kinase constituitive activity with it emiting strong growth-promoting signals in a dysregulated manner.