Breast Cancer Flashcards
What are the hormones that have important links to breast cancer and are influenced by hypothalamic light regulation?
GnRH, estrogen, progesterone, melatonin, serotonin, vitamin D
What is melatonin secreted by?
The pineal gland to initiate sleep by decreasing body temperature
How is melatonin produced?
Vitamin D can stimulate tryptophan –> serotonin –> which is converted to N-acetyllserotonin by AANAT (rate limiting step) –> melatonin by H1OMT
How is there a relationship between breast cancer and melatonin?
Melatonin is a regulator of ERalpha and estrogen production
How does vitamin D stimulate tryptophan production?
HRE for vitamin D upregulates Trp hydrozylase
What happened to melatonin production of night shift workers?
They had drastic reduction in melatonin production
What were the effects of night shift work on estrogen levels?
See production of estradiol as almost double the amount in control for pre menopausal women
How does melatonin modulate the ERalpha pathway?
Melatonin binds to Mt1 receptor, which inhibits estrogen, ERalpha, and calmodulin –> reduction of cAMP –> blocks cell invasion and metastasis and matrix metalloproteases
What type of receptor is the melatonin receptor?
A GPCR g alpha i –> reduction of cAMP levels
Where is most serotonin produced?
In the cells of the gut, the rest is produced in the CNS where it regulates mood, appetite, and sleep
What does exposure to light do to serotonin production?
Increases serotonin production, you need 480 nm light to induce serotonin production.
What are the effects of vitamin D on cancer cells?
- inhibits ERa in cancer cell –> inhib proliferation
- Inhibits aromatase in cancer cell–> less E signaling
- Inhibits COX-2 in cancer cell (converts arachidonic acid to PGE, which contributes to proliferation)
- Inhibits IL-6 and TNF-a production by macrophages –> less proliferation
- Inhibits aromatase in stromal fibroblasts
- Inhibits cox-2 stromal fibroblast cells
- Inhibits aromatase in adipocytes
