Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Stem cells, Ageing and Cancer > Post-embryonic growth and cancer > Flashcards

Post-embryonic growth and cancer Flashcards

1
Q

over what sort of range does patterning occur in early development?

A

In early development cell patterning events like the action of diffusing morphogens functions over a limited range, usually not much more than 100 cell diameters.
- Patterning is done on a small scale

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what determines the final shape and size of an organism?

A
  • The final shape and size of an organism is determined afterwards by differential growth
  • Growth is a key factor in determining shape
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what are the 3 ways in which growth occurs?

A
  1. cell proliferation (hyperplasia) - most cases
  2. cell enlargement (hypertrophy) - e.g. cardiac hypertrophy, skeletal muscle
  3. accretion - deposition of ECM between cells to cause enlargement e.g. how bones grow
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what drives cell proliferation?

A

the cell cycle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what are the phases of the cell cycle?

A

The cell cycle consists of 4 phases and a resting phase (G0)
- G1 (gap) – cell enlarges
- S-phase (synthesis) – DNA is replicated
- G2 – rest
- Mitosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what phases of the cell cycle constitute interphase?

A

G1, S-phase, G2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what is the resting phase (G0) of the cell cycle?

A

Fully differentiated cells reside in G0 and do not proliferate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what drives the cell cycle?

A
  • Cell cycle is driven by cyclins which associate with and activate cyclin-dependent kinases (Cdks)
  • Cdks control proteins that trigger events of each phase by phosphorylation
  • Cyclins fluctuate in concentration during cell cycle
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what cyclins and cdks are active in G1?

A

Cdk4/6 and cyclin D promote G1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what cyclins and cdks are active in S-phase?

A

Cdk2 and cyclin E promote S phase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what cyclins and cdks are active in G2?

A

Cdk2 and cyclin A drive G2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what cyclins and cdks are active in mitosis?

A

Cdk1 and cyclin A/B drive mitosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

how are cyclins and cdks controlled?

A

Growth programmes have some intrinsic and extrinsic control in the early embryo
- Different tissues are established, and with their establishment they acquire growth programs that are intrinsic to that tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

how does the Drosophila embryo develop (up to 14th cell cycle)?

A

Drosophila are under intrinsic control of cell division:
- Drosophila initially develops as a syncytium - Syncytium is a single cell with multiple nuclei
- The nuclei of the syncytium go through rapid synchronous cell cycles consisting of only S and M phase
- At the 14th cell cycle (1000s of nuclei), the cycle lows and G2 phase is introduced
- Many nuclei migrate to the periphery of the syncytium and become surrounding by a cell membrane = cellularisation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what is a syncytium?

A

Syncytium is a single cell with multiple nuclei

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what is cellularisation?

A

The separation of a syncytium into individual cells by a cell membrane surrounding the nuclei

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

how do each of the cells in the Drosophila embryo acquire its own division rate?

A

Depending on is precise position in the A/P and D/V coordinate system, each cell will acquire its own cell division rate
- groups of cells with similar fates and division cycles form mitotic domains, which have their own growth programme
- cell division in these domains is controlled by String protein
- from 1-13 divisions, String is uniformly distributed and supplied maternally for rapid divisions
- after 13th division, String is controlled by patterning genes to set up A/P and D/V axes
- patterning genes control String expression to form different mitotic domains, each of which has its own cell division programme and rate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what is string?

A

String is a phosphatase, which by activating Cdks, controls cell division rates in mitotic domains

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what controls string?

A

Patterning genes directly control String expression
- combinations of the patterning genes form different mitotic domains and tissues
- there is a direct link between patterning genes via string expression to the control of specific cell division programmes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

when is string controlled?

A

division 1-13, String is not specifically controlled and is expressed uniformly amongst all tissue types to promote rapid division

after division 13, String is controlled by patterning genes to ensure its expression at different levels in different tissues, thus meaning each tissue acquires its own division rate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what signalling pathways are involved in the formation of mitotic domains?

A

Signaling pathways like Wnt, Hh, Bmp, EGF, FGF, IGF, Hippo, Tor are involved

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what is the exception to the Drosophila intrinsic control of cell division?

A

the mesoderm is one of the first domains to express string but the 10th domain to divide
- So in spite of having string present these cell do not divide.
- This has been found to be due to a protein call tribble, an inhibitor of string.
- Tribble is induced by mesoderm-inducing genes.
- The mesoderm needs to invaginate and formation of this ventral furrow can be inhibited by cell division, thus tribble functions to promote invagination by preventing cell division at an inappropriate time.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what is tribble?

A

tribble is a string inhibitor which inhibits cell division of the mesoderm, enabling the mesoderm to invaginate the embryo

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

how is organ size controlled?

A

growth control of an organ depends on the organ itself
- Limbs undergo intrinsic control of growth
- spleen is under systemic/extrinsic patterning control

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

are growth programmes dynamic/flexible?

A

yes, growth programmes are flexible
- e.g. if liver is removed in an operation, liver will enter a growth programme to reform to its original size
- insults can alter the growth programme of organs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

is organ size determined by cell number?

A

no, organ size is instead determined by absolute dimensions and morphogen gradients:
- Ploidy affects cell size but not overall size of animal
- Steepness of morphogen gradients determines growth of organs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what are the 2 key growth control pathways?

A
  1. TOR pathway
  2. Hippo pathway
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

how does the TOR pathway control growth?

A

TOR promotes growth and increases cell size:
- When rapamycin inhibits TOR, cells are smaller
- when TOR is active, cells grow larger

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

how does the Hippo pathway control growth?

A
  • When the hippo pathway is inactive, the transcription factor Yki/Yap/Taz is in the nucleus stimulating growth and cell survival
  • When hippo pathway is active, Yki/Yap/Taz is excluded from the nucleus to inhibit growth

Hippo/ Mst1/2 integrates various signals to create a ‘stop growing’ signal

active Hippo = inhibits growth
inactive Hippo = promotes growth

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

what is the vertebrate counterpart of Hippo?

A

Mst1/2

31
Q

what is the vertebrate counterpart of the Yorkie (Yki) transcription factor in the Hippo pathway?

A

Yap/Taz

32
Q

what is Hippo?

A

hippo is a kinase

33
Q

what happens when hippo is active? what does it promote?

A

when it is active it blocks entry of the Yorkie TF in Drosophila
- when hippo kinase is active, the TFs are excluded from the nucleus and growth is inhibited, apoptosis promoted

34
Q

how is hippo activated?

A

Merlin/Expanded/Kibra can activate hippo via cell-cell contact, cell polarisation

35
Q

what happens when hippo is inactive? what does this result in?

A

When hippo is inactive, the TFs (Yki) are in the nucleus and stimulate growth, apoptosis is suppressed

36
Q

how does inactivation of hippo occur?

A

Inactivation of hippo can occur due to mechanical stress and other signalling pathways such as Wnt, Hh, BMP

37
Q

what occurs when hippo/Mst1 is mutated/deficient in model organisms?

A

Invertebrate: if hippo is mutated/deficient in a fly, there is no longer growth restriction as Yki is active in the nucleus, and the mutant fly has large outgrowths compared to the wildtype

vertebrate: if there is an Mst1/Mst2 mutant in mice, there is no longer control of liver size, so the liver is much larger as Yap/Taz promote excessive growth

38
Q

are growth rates uniform across all organs?

A

no, growth rates of different body parts are not uniform
- Head is massive compared to rest of the body at birth

39
Q

what controls the size of organisms/organs?

A

Size is controlled by the rate and duration of growth
- e.g. Boys and girls grow rapidly initially, and then growth rate drops over time up to a point
- When puberty starts, another growth spurt occurs (boys later than girls)

40
Q

what determines the size of an adult fly?

A
  • Size of adult is determined by the size of the larva
  • The size of the larva is determined by insulin signaling, which affects both the duration and rate of larval growth
  • Insulin-deficient larvae are much smaller and have fewer cells compared to normal flies
  • At a certain size, the larva Edcyson induces metamorphosis
41
Q

what factors/pathways are key in determining the size of an organism?

A
  1. Insulin-like growth factor (IGF1 and IGF2)
  2. Growth hormone (GH)
42
Q

what controls the growth of mammals?

A

In mammals growth occurs in a specific pattern - it is under hormonal control

43
Q

what hormone is important for both embryonic and adult growth?

A

IGF1 and IGF2

44
Q

what hormone is important for post-embryonic growth?

A

Growth hormone

45
Q

what happens if IGF1/IGF2 is mutated?

A

Mutations in IGF1 and IGF2 result in embryos being much smaller in size

46
Q

how does growth hormone (GH) signalling occur?

A

GH is the driver of growth, via activation of IGF-signalling
- Many of the effects of GH are mediated via IGFs

47
Q

what feedback mechanisms are involved in GH signalling?

A
  • The production of GH in the pituitary is stimulated by growth hormone releasing hormone (GHRH) and inhibited by somatostatin both from the hypothalamus.
  • GH negatively feeds-back on its own production, it promotes production of somatostatin and inhibits GHRH.
  • IGF also downregulates GH signalling to ensure controlled growth rate
48
Q

how does the maternal environment influence growth?

A
  1. Genetics: if Shetland pony is crossed with a Shire, if the mother is a Shire the foal is larger, if mother is shetland the foal is smaller, but both will grow to same size in middle of shetland and shire
    - mother determines the growth of a foetus
  2. Environmental/maternal conditions will also affect growth in the womb, and may have significant consequences post-embryonically
    - In human it has been shown that inadequate growth in utero (due to e.g. famine or bad diet) can lead to lifelong consequences such as coronary heart disease
49
Q

give examples of how the maternal environment influences growth?

A

In human it has been shown that inadequate growth in utero (due to e.g. famine or bad diet) can lead to lifelong consequences such as coronary heart disease

Dutch famine in world war II, in the winter from 1944-45:
- The result of this was a short but severe caloric restriction.
- Although early exposed babies recovered in weight and size, lifelong consequences can be seen.
- These people had an increased risk of obesity diabetes and probably also coronary heart disease.

50
Q

do all animals directly develop into an adult?

A

Many animals do not directly develop into an adult form, but rather form quite specialised embryonic and larval stages that, at a particular point in their development, undergo a radical change into an adult form: Metamorphosis

In many insects (Drosophila, butterfly) develop a larval form; adult structures hidden as imaginal discs inside the larva

51
Q

what is metamorphosis?

A

the process of transformation from an immature form to an adult form in two or more distinct stages
- e.g. Drosophila form embryonic and larval forms before undergoing a radical change into an adult

52
Q

are signals in development short range or long range?

A

they are short range and small in size, as the embryo is only a few cells

53
Q

are signals in post-embryonic development short range?

A

no, signals in post-embryonic development are coordinated by influences from the environment
- these influences act on the CNS, leading to hormone production on a whole organism level

54
Q

how do arthropods undergo post-embryonic development?

A

arthropods have to molt in order to grow
- The cuticle of arthropods is rigid and does not allow for growth to occur, therefore the larvae of insects have to molt in order to grow.
- This molting process is called ecdysis, the intermold stages are called instars.
- In the developmental model Drosophila melanogaster, 1st, 2nd and 3rd instar larvae are formed before pupation

55
Q

what are examples of post-embryonic development?

A

molting

metamorphosis

56
Q

what is the process of ecdysis?

A
  1. *Molting is initiated by activation of stretch receptors in the cuticle
  2. this leads to release of protothoracicotropic hormone (PTTH) from the corpus alatum which in turn leads to release of ecdyson from the protothoracic gland
  3. Under the influence of ecdyson molting occurs.
  4. First the cuticle separates from the epidermis.
  5. While the original cuticle is still present the freed epidermal cells proliferate, secrete a fluid that forms a barrier, and start secreting new cuticle.
  6. Only after this stage the old cuticle will be shed
57
Q

how do insects control metamorphosis?

A
  1. Metamorphosis in insects occurs under the influence of a variety of environmental cues like nutrition, temperature and light
  2. These cues are integrated in the CNS and, leading to release of PTTH which acts on the protothoracic gland and corpus alatum, leading to release of juvenile hormone and ecdysone
  3. juvenile hormone prevents metamorphosis whereas ecdysone promotes it.
    - Balance of the 2 hormones
58
Q

how do tadpoles control metamorphosis?

A

In frog tadpoles a similar change in the balance of prolactin and thyroxine causes metamorphosis:

  1. this balance can be changed by environmental cues that act via the hypothalamus which secretes CRH (corticotropin-releasing hormone)
  2. CRH in turn acts on pituitary cell and causes secretion TSH (thyroid-stimulating hormone).
  3. TSH acts on the thyroid and stimulates release of thyroxin (T4T3)
  4. Thyroxin actually positively feeds back on itself, this means that if a certain level is reached, the process of metamorphosis becomes irreversible.
    - Prolactin can prevent metamorphosis
    - Thyroxin has different effect on different tissues, whereas it causes growth of the limbs it causes degeneration of the tail.
    - It also modulates responsiveness to other signals like estrogen
59
Q

why must creation and maintenance of tissue be under strict control?

A
  • The creation and maintenance of tissues requires strict controls.
  • Cell loss and generation of new cells should be tightly balanced.
  • A small imbalance between gain and loss of cells can over time create a large effect.
  • must be controlled in order to prevent uncontrolled growth and cancer
60
Q

what is cancer?

A

Cancer can be considered to be a disease where this growth control is lost
- Cancer is associated with a failure in the normal differentiation process that occurs during development or maintenance of tissues
- cancer is connected to mutations that are acquired by the tumor cells, however this does not always apply 100%

61
Q

what sorts of tissue commonly form cancer? why?

A

Tissues that are continuously replaced and have a quite active cell population are most commonly connected to cancer
- This is because these cells are already proliferating – one step closer to uncontrolled
- also, each time the genome is copies there is a chance for mistakes to occur that are oncogenic.

62
Q

what are examples of common tissues that form cancer?

A

epithelia and blood - overall 88% of cancers occur in epithelia or blood

63
Q

what is teratoma cancer?

A
  • Teratoma cancer cells are similar to embryonic cells and can give rise to tissues from all three germ layers, ectoderm mesoderm and endoderm.
  • In mice, murine teratoma cells can be transplanted to embryos and these cells can participate normally in the formation of an animal.
  • Thus they are not permanently transformed – epigenetic modification rather than mutation – reversible
64
Q

do all mutations lead to cancer?

A

Not all mutations lead to cancer, only a subset of genes in the genome that are mutated can lead to cancer

65
Q

what 3 factors cause loss of growth control?

A
  1. activation of oncogenes
  2. inactivation of tumour suppressor genes
  3. response to false/faulty developmental/growth signals
66
Q

what are proto-oncogenes? how are they involved in loss of growth control?

A

Loss of growth control can be the result of activating mutations in certain genes, these are called proto-oncogenes
- once activated, they become oncogenes and promote uncontrolled growth, tumourigenesis and cancer

67
Q

what are examples of proto-oncogenes/oncogenes?

A

Ras, Raf, Epidermal Growth Factor Receptor (EGFR), Myc, Smo

68
Q

what are tumour-suppressor genes? how are they involved in cancer?

A

Cancer can be the result of loss of genes that normally inhibit growth these are tumor suppressor genes
- tumour suppressor genes usually regulate/inhibit growth, so if they are inappropriately inactivated by mutation, this leads to uncontrolled growth cancer

69
Q

what are exaples of tumour suppressor genes?

A

Retinoblastoma (Rb), p53, PATCHED, adenomatous polyposis coli (APC), Von Hippel Lindau (VHL)

70
Q

how are developmental signals involved in cancer?

A

a number of negative regulators of developmental signal transduction pathways are involved: Patched regulating hedgehog signal, and APC regulating Wnt
- These pathways also play a role in stem cell renewal,
- False developmental signals result in the misregulation of proliferation and differentiation of stem cells, leading to cancer.

In very many if not all cancers there appears to be a failure to differentiate and the cells appear to be responding to false developmental/growth signals

71
Q

what developmental signals are implicated in cancer?

A
  • Activated Wnt - Colon cancer, Hepatocellular cancer
  • Activated Hedgehog - Basal cell carcinoma, Medulloblastoma
  • Activated Nodal - Melanoma?
  • Activated Notch - Leukemia
  • Activated EGF - Lung cancer, Breast cancer
72
Q

what is the role of BRCA1, BRCA2 and p53?

A

these genes maintain genome stability

73
Q

how are BRCA1, BRCA2 and p53 implicated in cancer?

A
  • Mutations in these genes lead to genome instability
  • => Resulting mutations may lead to aberrant developmental signals

It is important to realise that mutations in tumor suppressors of oncogenes that lead to genome instability (eg BRCA2, ATM) are unlikely to directly cause cancer, we expect that these lead to mutations that again interfere with normal growth control i.e. often with the signals above.

Stem cells, Ageing and Cancer (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions