Molecular background of tumorigenesis. Flashcards Preview

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Flashcards in Molecular background of tumorigenesis. Deck (15)
1

Difference between just immortalized cells and transformed cells

Immortalized
can replicate indefinitely, but don't metastasize within the animal,
Still only grow in a monolayer and need attachment, still subjected to contact inhibition

Transformed
Immortalized and also are not subject to attachment or contact inhibition,
will proliferate while floating and in the absence of growth facto

2

Senescence

induced by telomere shortening
or
tumor suppressor factors

mainly,
p53
or RB

p53,
activates p21
and
disinhibits Rb

3

multiple mechanisms how p53 inhibits tumors

Prevents vascularization

Causes cell cycle arrest and senescence

Initiates DNA repair pathways

Induces Apoptosis

4

DNA viruses that can inhibit p53

HPV E6 inhibits p53
E7 inhibits Rb

Adenoviruses inhibit p53 and Rb

SV40, simian vacuolating virus 40, a polyoma virus, other polyoma viruses also inhibit p53 and Rb

5

How does Rb inhibit proliferation?

Binds to E2F transcription factors (a family of TFs), preventing them from activating cell cycle genes.

6

What are the proteins that specifically inhibit p53 from those viruses?

E6 from HPV

LT

E1B

7

What do the adenoviral proteins E1A and E1B inhibit?

E1A inhibits RB

E1B inhibits P53

8

what are 3 ways tumor cells bypass senescense

inhibiting p53
inhibitin Rb

Expressing telomerase

9

What RNA viruses are tumorviruses?

Retroviruses, by integration of oncogenes into genome.

Rous Sarcoma Virus

HTLV-1

10

What is the oncogene in Rous Sarcoma Virus

v-src, which is a mutated version of the somatic c-src non-receptor tyrosine kinase. c-src is a normal host proto-oncogene.

induces motility, proliferation, survival.

11

What kind of proteins are coded by human proto-oncogenes?

Growth factors

Tyr Kinase receptors

Intracellular signaling proteins,
non-receptro tyroskine kinases
ser/thr kinases

Transcription factors

Nuclear TF receptors,

Positive cell cycle regulators, cyclins

Inhibitors of Apoptosis, BCL2

12

How do protooncogenes become oncogenes

By activating mutations, basically list any way a mutation can increase gene activity.

Point mutations

Gene amplification

Chormosomal translocation, different regulation, increased expression

Deletions or repressor regions

Insertion of a viral DNA hyperactive promoter region in front of the gene.

13

How can Ras be permanently activated via mutation

A point mutation that changes Gly -> Val

Ablates its GTPase activity, thus it binds GTP becoming active and then never cleaves it to GDP to inactivate itself.

14

Human tumor viruses

EBV

HBV, HCV

HTLV-1

HPV many strains

Kaposi sarcoma virus

Merkel cell polyomavirus

15

Random animal tumor diseases

Tasmanina devil facial tumor disease, trasmitted by biting

Canine tranjsmissible veneral tumors