Breast Cancer Flashcards
how does exposure to increased light at night affect sleep and circadian rhythm?
disrupts normal sleep and circadian rhythm
does melatonin increase/decrease with disrupted sleep and circadian rhythm?
decreases melatonin levels
why is melatonin known as the hormone of darkness?
because it is secreted only at night
what is the precursor of melatonin?
serotonin, its secretion requires the absence of 480 nm light
how is melatonin secreted in mammals?
into the blood by the pineal gland to initiate sleep and regulate circadian rhythms
WHO has determined that we spend…
90% of our time indoors
what wavelength is needed for serotonin production?
480nm, while melatonin production is inhibited by the presence of 480 nm light
what two NT’s does light exposure regulate?
serotonin and melatonin
what wavelength is required for vitamin D synthesis?
requires 295nm UVB light, challenging to produce indoors becuz indoor lighting lacks this wavelenth (found in sunlight)
The hormones with important links to breast
cancer and are influenced by hypothalamic light
regulation (via SCN) include…
GnRH, estrogen, progesterone, melatonin, serotinin, vitamin D
how does melatonin inhibit estrogen response pathway?
by binding to Mt1
how do the antiproliferative effects of melatonin occur in breast cells?
through activation of melatonin receptors (Mt1, a GPCR) expressed in both healthy and cancer breast cells
how does melatonin suppress estrogen receptor (ER alpha +) human breast cancer cells?
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
what are the anti-metastatic actions of melatonin?
blocks MAPkinase pathways and the expression of matrix metalloproteinases
how does melatonin down regualte growth factor pathways in breast cancer?
down regulates growth factor athways that support cell proliferation and survival, thereby inhibiting cancer growth
what evidence supports the link between artificial light at night (LAN) and breast cancer risk?
experimental evidence in rats and humans, showing that LAN induced disruption of nocturnal metatonin signal activates human breast cancer growth, metabolism and signaling
when is melatonin primarily produced?
at night, peaking between 2am and 5am
what does decreased natural bright daytime light exposure lead to?
increased breast cancer risk
what have studies shown about vitamin d?
that higher levels of vitamin D are associated with a decreased risk for breast cancer
low natural light exposures results in
low vitamin D and is noted in most people in the western world - suggests we should expose ourselves to more natural light
how does vitamin D inhibit breast cancer cell proliferation in the estrogen pathway?
inhibits estrogen receptor alpha (ERa) and aromatase in the estrogen pathway
what effect does vitamin D have on COX-2 in breast cancer cells surrounding adipose fibroblasts?
inhibits COX-2 in both cancer epi cells and breast adipose fibroblasts surrounding the tumor, thereby inhibiting breast cancer cell proliferation
besides the estrogen pathway and COX-2, what additional pathway does vitamin D affect to inhibit cancer?
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
how does vitamin D impact breast cancer cells regardless of their estrogen receptor status?
inhibitory effects are independent of estrogen receptor status, affecting both ER+ and ER - breast cancer cells through various pathways
what are the roles of vitamin D in breast cancer?
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
how does periodic sunlight exposure during the day influence the bodys natural levels of serotonin, melatonin and vitamin D?
regulates them
what association has been found between breast cancer and levels of melatonin serotinin and vitamin d?
breast cancer has been associated with low levels of all three
Classic circadian rhythm studies have also utilized the rhythmic changes in
__________ levels as biomarkers of the
circadian clock
temperature, melatonin, serotonin, and vitamin D
changes in human exposure to environmental light affects…
biological rhythms
what key hormones does light exposure and circadian rhythm disruption affect the metabolism of?
GnRH, estrogen, progesterone, testosterone, vitamin D and melatonin
what NT’s are affected?
dopamine and serotonin
how do light and CR impact micronutrients?
alters micronutrients such as iron
consequences of changes induced by light exposure?
increase the risk of chronic diseases including breast cancer
how does vitamin D influence serotonin synthesis in the brain?
activates the transcription of the initial serotonin-synthesizing gene tryptophan hydroxylase in the brain at the vitamin D response element
how do melatonin and vitamin D affect estrogen signalling?
both down regulate estrogen signaling, decreasing cancer risk
what is the potential link between low elvels of vitamin D, serotonin, melatonin and increased estrogen signaling?
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
