Growth Control (14) Flashcards

1
Q

What are the three main factors that control growth?

A

1- Cell lineage
2- External/ Diffusible Factors
3- Cell-cell/ Cell- ECM interactions

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2
Q

What is cell lineage?

A

Internal control of G1/S transition

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3
Q

When does apoptosis occur?

A

During normal development and also in adulthood

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4
Q

Why does apoptosis occur?

A

It is usually a result of checkpoint error during DNA replication/ cell cycle

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5
Q

What are three examples of apoptosis during normal development?

A

1- Formation of the digits
2- Epithelial cells during palate fusion
3- Neurons in developing brain

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6
Q

Name two examples of apoptosis that occurs in normal adult cells?

A

1- Lining of the gut

2- Mammary tissue post-lactation (due to hormone deprivation)

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7
Q

What is the fol of apoptosis during the development of the brain?

A

To control the number of neuros. Cell death matches the number of nerve cells to number of target cells.

Trophic signals are required for cell survival.

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8
Q

Describe the morphology that an apoptotic cells?

A

They shrink, then form membrane blebs and then fragment, releasing small membrane-bound apoptotic bodies that are phagocytosed by macrophages

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9
Q

What happens to necrotic cells?

A

They swell and burst

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10
Q

Which cells are usually associated with inflammation….Necrotic cells or apoptotic cells?

A

Necrotic cells

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11
Q

What is Bad allowed to do when there are no trophic factors present?

A

Bad can interact with the anti-apoptotic proteins….Bcl2 and Bclxl

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12
Q

Where are Bcl2 and Bclxl located?

A

Outer mitochondrial membrane

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13
Q

What does the interaction of Bad with Bcl2 and Bclxl inhibit?

A

The interaction of Bcl2 and Bclxl with Bax is inhibited?

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14
Q

What happens when the Bax is not inhibited?

A

Bax containing ion channels form and the release of cytochrome C from the mitochondria into the cytosol. This results in the activation of a series of cysteine proteases called caspases.

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15
Q

What is the action of caspases?

A

They digest important intracellular structural proteins such as the nuclear lamins and cytoskeletal proteins leading to the cells demise and fragmentation

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16
Q

What is terminal differentiation?

A

Cell stops dividing and express a novel set of genes for specialized function

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17
Q

What is senescence?

A

Ceasing cell division due to absence of telomerase

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18
Q

What is telomerase?

A

A ribozyme (part protein, part RNA)

It adds a 6 base repeat to parental DNA strand and permits the completion of synthesis of the lagging strand

19
Q

True or False: Most adult somatic cells have telomerase.

A

False….most lack telomerase

20
Q

How is senescence activated?

A

When telomeres get too short, p53 is activated and then this activates p21 CDK inhibitor

21
Q

What is the function of p21 CDK inhibitor?

A

It blocks the cell in G1t

22
Q

Give an example of a growth factor that acts locally

A

Platelet derived growth factor is released from activated platelets and this stimulates wound repair

23
Q

Give an example of a growth factor that works systemically?

A

Erythropoietin which is synthesized in the kidney…this stimulates RBC differentiation in bone marrow

24
Q

What is the importance of anchorage- dependent cell growth?

A

It provides cell surivial signals to preventapoptosis

25
Q

What is contact inhibition?

A

Cell-density dependent growth inhibition (when the cells touch they stop growing)

26
Q

Nerve and cardiac muscle cells are examples of _______ cells.

A

Permanent cells

27
Q

If cells regenerate, what do they regenerate from?

A

Undifferentiated stem cells. They replace differentiated cells that cannot divide

28
Q

Describe the organization of the skin epidermis is maintained?

A

1- Stem cells attached to basal lamina continue to divide as long as the cells are anchoraged

2- Decrease in integrins/ Focal adhesions/ hemi-desmosomes

3- Detached cells stop proliferation and this drives differentiation

4- Increased caderins/keratins/ desmosomes

5- Provides strength/ barrier characteristics of skin

6- Cells die/ flatten but continue to function as barrier

7- Sloughed off and replaced

29
Q

Growth control is a balance of _______ and _________ signals.

A

Stimulatory and inhibitory

30
Q

What is different in transformed cancer cells?

A

Do not senesce

Lack growth factor dependence

Lack anchorage dependence

No cell-cell contact inhibition

31
Q

What are the two main classes of mutation that affect the function of proteins involved in growth regulatory signal transduction pathways?

A

Oncogenes and tumor suppressor genes

32
Q

What are oncogenes?

A

Mutated or overexpressed versions of genes normally found in cellular genomes

33
Q

What where the first discovered oncogenes?

A

Viral oncogenes in retroviruses

34
Q

Generally, what are the functions of proto-oncogenes?

A

They are proteins that normally stimulate growth/ cell proliferation

2- Conversion to an oncogene result in

35
Q

True or False: Mutation of a single allele of a proto-oncogene can cause abnormal growth.

A

True

36
Q

What is the normal function of tumor suppressor genes?

A

Normally function to oppose the activity of proto-oncogenes…they normally inhibit growth

37
Q

How many alleles of a tumor suppressor gene must be mutated or deleted before uncontrolled growth occurs?

A

Both alleles

38
Q

True or False: First mutation/ deletion of Tumor suppressor genes is often inherited- individuals are predisposed to developing cancer.

A

True

39
Q

What is retinoblastoma (Rb)? What happens when it is lost?

A

A negative regulator of gene transcription.

When it is lost there us unregulated transcription

40
Q

What are the functions of p53?

A

Induces synthesis of a G1, CDK inhibitor (p21)

Blocks Rb phosphorylation

May induce apoptosis/ senescence

41
Q

What does HPV produce that inhibits Rb and p53?

A

E6= Rb

E7= p53

42
Q

What does SV40 virus produce that bind Rb and p53?

A

Large T antigen

43
Q

What are the general stages of cancer progression?

A

Loss of cell division/ growth control

Ability to invade and metastasize