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Bio 432 > Environment (Light) and Breast Cancer Cont. - Final Exam > Flashcards

Environment (Light) and Breast Cancer Cont. - Final Exam Flashcards

1
Q

What neurotransmitter/hormone is part of the pathway for melatonin biosynthesis?

A

Serotonin

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2
Q

What has vitamin D been found to activate?

A

The transcription of the initial serotonin – synthesizing gene tryptophan hydroxylase

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3
Q

What 2 factors down-regulate estrogen signalling and what is the result?

A
  1. Melatonin
  2. Vitamin D
    - -> Result = decrease in breast cancer
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4
Q

What does low levels of serotonin and vitamin D, coupled with increase in LAN and low melatonin levels lead to?

A

Increases levels and effects of estrogen, thus increasing the risk of breast cancer

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5
Q

What is serotonin a local regulator of?

A

Mammary gland epithelium

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6
Q

How many serotonin receptors exhibit different expression patterns in breast caner specimens?

A

4

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7
Q

What does serotonin regulate and what does it initiate?

A
  • Regulates = lactation

- Initiates = transition into the earliest phases of apoptosis

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8
Q

What does serotonin regulate in the breast for production?

A

Ca

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9
Q

When does massive cell shedding and cell death occur?>

A

During early involution

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10
Q

What does serotonin induce?

A

Cell death of normal mammary epithelial cells in vitro

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11
Q

What seems to be resistance to serotonin (5-HT)-induced cell death?

A

Breast cancer cells

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12
Q

Mt1

A

Melatonin receptor 1

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13
Q

What receptor family is Mt1 apart of?

A

GPCR

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14
Q

What does melatonin-mediated cyclical regulation of GnRH mRNA expression may involve?

A

PKC and the extracellular signal-regulated kinase 1 & 2 pathways
- but not the PKA pathway

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15
Q

What does melatonin regulate?

A

GnRH

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16
Q

What does GnRH regulate and how?

A

Estrogen hypothalamic-pituitary-gonadal axis via LH and FSH

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17
Q

What does LH regulate?

A

Progesterone

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18
Q

What are 5 approaches to look at LAN effect on the circadian rhythm that accounts for part of the breast cancer burden?

A
  1. Other studies looking at shift work
  2. Epidemiology comparing different areas of the world
  3. Direct evidence that light inhibits melatonin synthesis
  4. Animal models
  5. Melatonin signalling pathways
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19
Q

What do you have an automatic risk for if you dont have children and why?

A

Breast cancer

- You need to interrupt the menstrual cycles with pregnancy

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20
Q

What is a risk for breast cancer in shift working women?

A

Urinary melatonin metabolite in night nurses significantly ~40% lower on both work and off days compared to dayshift nurses

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21
Q

What could different sensitivity to shift work be associated with?

A

Genetic background

22
Q

How are the effects of the melatonin signals mediated?

A

Through a mechanism involving the activation of melatonin receptors

23
Q

Where are melatonin receptors expressed? (2)

A
  1. Healthy human breast cells

2. Cancer cells

24
Q

The anti-metastatic actions of melatonin involve what?

A

Blockage of…

  1. P38 phosphorylation
  2. Expression of matrix metallproteinases
25
Q

What does melatonin downregulate? (2)

A

Growth factor pathways…

  1. Supporting cell proliferation
  2. Survival
26
Q

What is melatonin an inhibitor of?

A

Breast cancer

27
Q

How does melatonin downregulate the levels of estrogen?

A

By inhibiting aromatase

28
Q

How can melatonin repress genomic instability?

A

Through its suppression of telomerase activity

29
Q

What specific important tyrosine kinase is being targeted by serotonin?

A

Src

30
Q

How does melatonin inhibit protein degradation, via what?

A

By activating ubiquitin pathways via GSK3 beta

31
Q

What does progesterone induce and why?

A

Development of breasts in preparation of lactation

32
Q

What does PRA and PRB regulate?

A

Proliferation and differentiation in the normal mammary gland

33
Q

PRA

A

Progesterone receptor A

34
Q

PRB

A

Progesterone receptor B

35
Q

Is progesterone part of the circadian rhythm?

A

Yes

36
Q

How do you get expression of progesterone?

A

Down regulation of core clock gene Bmal1

37
Q

What has been demonstrated to be a potent endocrine oscillators?

A

LH

38
Q

What does LH dramatically increase?

A

Progesterone biosynthesis

39
Q

What hormone controls LH?

A

GnRH

40
Q

What is progesterone receptor used as?

A

Biomarker for estrogen-alpha function and breast cancer prognosis

41
Q

What is progesterone affected by?

A

Light

42
Q

What does progesterone activate?

A

Progesterone receptors

43
Q

What are the 4 pathways ER-alpha and PR are able to activate?

A
  1. Mitogen-activated protein kinase (MAPKs)
  2. JAK/STAT
  3. Src
  4. Phosphatidylinositol-3-kinase (PI3K)
44
Q

What does protein kinase A and PAK do to ER-alpha?

A

Phosphorylate it in order to activate it

45
Q

What 2 receptors is cAMP involved in activation?

A
  1. ER-alpha

2. PR

46
Q

What activates ER-alpha by cAMP signalling and what does it lead to?

A
  • CARM1

- Leads to phosphorylation

47
Q

CARM1

A

Coactivators-associated arginine methyltransferase-1

48
Q

What happens once ER and CARM1 is phosphorylated?

A

They can interact and can bind to the DNA to regulate target genes

49
Q

E2

A

Estradiol

50
Q

HB

A

Heparin binding

51
Q

What is progesterone regulated by?

A

Estrogen

52
Q

How does GnRH regulate estrogen?

A

Via LH

Bio 432 (19 decks)

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