Breast Cancer

Question 1

how does exposure to increased light at night affect sleep and circadian rhythm?

Answer 1

disrupts normal sleep and circadian rhythm

Question 2

does melatonin increase/decrease with disrupted sleep and circadian rhythm?

Answer 2

decreases melatonin levels

Question 3

why is melatonin known as the hormone of darkness?

Answer 3

because it is secreted only at night

Question 4

what is the precursor of melatonin?

Answer 4

serotonin, its secretion requires the absence of 480 nm light

Question 5

how is melatonin secreted in mammals?

Answer 5

into the blood by the pineal gland to initiate sleep and regulate circadian rhythms

Question 6

WHO has determined that we spend…

Answer 6

90% of our time indoors

Question 7

what wavelength is needed for serotonin production?

Answer 7

480nm, while melatonin production is inhibited by the presence of 480 nm light

Question 8

what two NT’s does light exposure regulate?

Answer 8

serotonin and melatonin

Question 9

what wavelength is required for vitamin D synthesis?

Answer 9

requires 295nm UVB light, challenging to produce indoors becuz indoor lighting lacks this wavelenth (found in sunlight)

Question 10

The hormones with important links to breast
cancer and are influenced by hypothalamic light
regulation (via SCN) include…

Answer 10

GnRH, estrogen, progesterone, melatonin, serotinin, vitamin D

Question 11

how does melatonin inhibit estrogen response pathway?

Answer 11

by binding to Mt1

Question 12

how do the antiproliferative effects of melatonin occur in breast cells?

Answer 12

through activation of melatonin receptors (Mt1, a GPCR) expressed in both healthy and cancer breast cells

Question 13

how does melatonin suppress estrogen receptor (ER alpha +) human breast cancer cells?

Answer 13

suppresses ERalpha mRNA expression and estrogen-induced transcriptional activity by ERa by activating MT1, which leads to the reduction of CAMP levels via Gai2 signalling

Question 14

what are the anti-metastatic actions of melatonin?

Answer 14

blocks MAPkinase pathways and the expression of matrix metalloproteinases

Question 15

how does melatonin down regualte growth factor pathways in breast cancer?

Answer 15

down regulates growth factor athways that support cell proliferation and survival, thereby inhibiting cancer growth

Question 16

what evidence supports the link between artificial light at night (LAN) and breast cancer risk?

Answer 16

experimental evidence in rats and humans, showing that LAN induced disruption of nocturnal metatonin signal activates human breast cancer growth, metabolism and signaling

Question 17

when is melatonin primarily produced?

Answer 17

at night, peaking between 2am and 5am

Question 18

what does decreased natural bright daytime light exposure lead to?

Answer 18

increased breast cancer risk

Question 19

what have studies shown about vitamin d?

Answer 19

that higher levels of vitamin D are associated with a decreased risk for breast cancer

Question 20

low natural light exposures results in

Answer 20

low vitamin D and is noted in most people in the western world - suggests we should expose ourselves to more natural light

Question 21

how does vitamin D inhibit breast cancer cell proliferation in the estrogen pathway?

Answer 21

inhibits estrogen receptor alpha (ERa) and aromatase in the estrogen pathway

Question 22

what effect does vitamin D have on COX-2 in breast cancer cells surrounding adipose fibroblasts?

Answer 22

inhibits COX-2 in both cancer epi cells and breast adipose fibroblasts surrounding the tumor, thereby inhibiting breast cancer cell proliferation

Question 23

besides the estrogen pathway and COX-2, what additional pathway does vitamin D affect to inhibit cancer?

Answer 23

cell cycle arrest, proapoptotic and pro-differentation actions and anti-inflammation

• these effects are observed in both estrogen receptor positive and estrogen receptor negative breast cancer cells

Question 24

how does vitamin D impact breast cancer cells regardless of their estrogen receptor status?

Answer 24

inhibitory effects are independent of estrogen receptor status, affecting both ER+ and ER - breast cancer cells through various pathways

Question 25

what are the roles of vitamin D in breast cancer?

Answer 25

1.It induces the expression of cell cycle arrest proteins and pro-
apoptotic cell death proteins (Bax and Bak).
2.It suppresses inflammation by inhibiting inflammatory enzymes
(such as COX-2).
3.It decreases the expression of aromatase, the final enzyme in the
synthesis of estrogen, by direct repression of transcription via
promoter II.
4.Also it down-regulates the expression of estrogen receptor-α,
thus attenuating the estrogen signal that stimulates proliferation

Question 26

how does periodic sunlight exposure during the day influence the bodys natural levels of serotonin, melatonin and vitamin D?

Answer 26

regulates them

Question 27

what association has been found between breast cancer and levels of melatonin serotinin and vitamin d?

Answer 27

breast cancer has been associated with low levels of all three

Question 28

Classic circadian rhythm studies have also utilized the rhythmic changes in
__________ levels as biomarkers of the
circadian clock

Answer 28

temperature, melatonin, serotonin, and vitamin D

Question 29

changes in human exposure to environmental light affects…

Answer 29

biological rhythms

Question 30

what key hormones does light exposure and circadian rhythm disruption affect the metabolism of?

Answer 30

GnRH, estrogen, progesterone, testosterone, vitamin D and melatonin

Question 31

what NT’s are affected?

Answer 31

dopamine and serotonin

Question 32

how do light and CR impact micronutrients?

Answer 32

alters micronutrients such as iron

Question 33

consequences of changes induced by light exposure?

Answer 33

increase the risk of chronic diseases including breast cancer

Question 34

how does vitamin D influence serotonin synthesis in the brain?

Answer 34

activates the transcription of the initial serotonin-synthesizing gene tryptophan hydroxylase in the brain at the vitamin D response element

Question 35

how do melatonin and vitamin D affect estrogen signalling?

Answer 35

both down regulate estrogen signaling, decreasing cancer risk

Question 36

what is the potential link between low elvels of vitamin D, serotonin, melatonin and increased estrogen signaling?

Answer 36

low levels of vitamin D may lead to low serotonin levels, which in turn low melatonin levels. this would increase estrogen signaling, leading to increased risk of breast cancer