Environmental Light and Breast Cancer Flashcards
amount of nm of light to make serotonin, melatonin and vitamin D
- need 480nm to make serotonin (noon sun vs. artificial); melatonin flip side has to be absent 490nm (i.e. light shuts down production/inhibits)
- need 295nm UVB to make vitamin D (so can’t make indoors)
what are circadian rhythms
•Physical, mental and behavioural changes that follow a roughly 24-hour cycle, responding primarily to light and darkness in an organism’s environment. They are found in most living things including animals, plants and many tiny microbes.
the study of circadian rhythms is called ______
The study of circadian rhythms is called chronobiology
light acts on the body by two pathways:
•the primary optic tract governs visual perception and responses whereas the retinohypothalamic tract governs circadian, endocrine and neurobehavioral functions
The retinohypothalamic tract is most sensitive to what kind of light
•The retinohypothalamic tract is most sensitive to blue light stimulation energy in the wavelength of roughly 459-485nm
light signals through what type of protein and is recieved by what type of cell in back of the eye
•Light signals through melanopsin protein that undergoes a chemical change when exposed to light received by intrinsically photosensitive retinal ganglion cells in the back of the eye
Some health effects of circadian clock de-regulation
10 of em
- Insomnia and sleep disorders
- Reduced alertness
- Poor cognitive and motor function
- Depression, bipolar disorder and seasonal affective disorder
- Cardio-vascular disease
- Altered hormone levels
- Obesity
- Early-onset diabetes
- Altered immune function
- Cancer – breast, prostate and colon
what is known as the hormone of darkness and is only secreted at night / is a precursor for serotonin
Melatonin
where does melatonin biosynthesis occur
in the pineal gland
melatonin is a regulator of what
- rate limiting step
- needs what vitamin
- melatonin is a regulator of ER alpha and estrogen production so clear relationship to breast cancer
- Rate limiting step uses serotonin to make Acetylserotonin
- Need vitamin D in the promoter region of tryptophan hydroxylase
what functions does the SCN perform / stimulates what hormones
- Once exposed to the first light each day, the clock in the SCN begins performing functions like raising body temperature and releasing stimulating hormones like cortisol
- The SCN also delays the release of other hormones like melatonin which is associated with sleep onset, until many hours later when darkness arrives
day shift vs night shift workers in terms of production of melatonin and serotonin
- Day shift workers who sleep at night have higher levels of melatonin whereas night shift workers had lower levels and its peak production was shifted
- Exposure to light and then darkness is a key factor in melatonin and sleep regulation and it has been recently found that exposure to light at night diminishes melatonin production
does melatonin inhibit or excite the estrogen response pathway
melatonin inhibits estrogen response pathway through binding to MT1
Melatonin modulated estrogen/ER alpha signalling pathway
- estrogen driven breast cancer and high levels of estrogen / estrogen receptor alpha
- melatonin will bind to a GPCR called mt1 (melatonin 1)
- will modulate effects of estrogen at the estrogen receptor by toning it down and decrease calmodulin actions on phosphorylation, also decreases the amount of estrogen being produced so is modulating aromatase (cells that produce aromatase are in granulosa cells in ovary - androgens produced at cortex can be converted by aromatase including visceral fat maybe surrounding breast) - the presence of melatonin downregulates production of aromatase
- decrease estrogen = decrease proliferation of breast epithelial cells
the antiproliferative effects of the melatonin signal are mediated through what mechanism
•the antiproliferative effects of the melatonin signal are mediated through a mechanism involving the activation of melatonin receptors (MT1 a GPCR) expressed in healthy human breast cells and cancer cells
what does melatonin suppressed in the estrogen receptor breast cancer cells
•in estrogen receptor (Era+) human breast cancer cells, melatonin supresses both ER alpha mRNA expression and estrogen-induced transcriptional activity of the ER alpha via MT1 induced activation of Gai2 signalling and reduction of cAMP levels
the anti-metastatic actions of melatonin involve what
- the anti-metastatic actions of melatonin involve the blockade of both p38 phosphorylation and the expression of matric metalloproteinases
- melatonin also down-regulates growth factor pathways supporting cell proliferation and survival
where is serotonin produced and what are it functions
- serotonin is a well-known neurotransmitter but also functions as a hormone
- most serotonin produced in cells of the gut – the remainder is synthesized in the central nervous system where it functions to regulate mood, appetite, memory and sleep
- modulation of serotonin levels is the major action of many antidepressants
when are the highest levels of serotonin / need what kind of light
- highest levels in the afternoon; need wavelength of light 480nm – derived from tryptophan (constituent of most protein-based foods)
- need blue light to increase serotonin
what is vitamin D essential for and what are other names for it
- vitamin D is essential for the formation of normal bones and teeth by maintaining normal blood levels of calcium and phosphorus but also many important effects including cell differentiation and development
- vitamin D has multiple names – can mean any of the fat soluble vitamins: D1, D2, D3 calcitriol = active vitamin
what is vitamin D structrually related to
•structurally related to steroids not a vitamin in this context because uses same type of high affinity nuclear receptor to affect transcription as steroids, and levels regulated (as compared to a vitamin that is typically from a diet and is a cofactor for some protein / enzyme)
role of vitamin D in breast cancer (what things does it inhibit)
- Vitamin D inhibits ER alpha and aromatase in the estrogen pathway and COX-2 of the prostaglandin pathway in BOTH cancerous breast epithelial cells and breast adipose fibroblasts surrounding the tumor – this inhibiting breast cancer cell proliferation
- Vitamin D also inhibits proliferation by additional pathways including cell cycle arrest, proapoptotic and prodifferentiation actions, anti-inflammation etc. which are active in both ER+ and ER negative breast cancer cells
vitamin D role in breast cancer (4 steps)
- It induces the expression of cell cycle arrest proteins and pro-apoptotic cell death proteins (Bax and Bak)
- It supresses inflammation by inhibiting inflammatory enzymes (such as COX-2)
- It decreases the expression of aromatase, the final enzyme in the synthesis of estrogen by direct repression of transcription via promoter II
- Also it down regulates the expression of estrogen receptor alpha thus attenuating the estrogen signal that stimulates proliferation
breast cancer has been found to be associated with low levels of what 3 things
serotonin, melatonin and vitamin D
