Upgrade to remove ads
Terms in this set (17)
What two cancers are best prevented in relation to nuclear receptors?
Breast and prostate cancers.
Most prevalent cancer in women
Breast cancer: more than double incidence of any other cancer but low and decreased death rate.
Risk factors for breast cancer
1. Gender (female/male bc of hormones), 2. age, 3. endocrine (less parity, early age at menarche, later age at first birth, later age at menopause-more cycle=more risk, exogenous hormone), 4. geographical origin, 5. geneetics, 6. nutrition.
Effect of estrogen on breast cancer
Exposure to estrogens (endo- and exogenous) major risk factors for breast cancer. Like a GF, affects breast, uterus, etc. to prepare for pregnancy. Longer cell reproduction/fast replication, less repair-->higher cancer risk
Hormones that act by interacting with nuclear receptors
Progesterone, cortisol, estradiol, T4, testosterone, 1,25D, retinoic acid (differentiation in fetus, needs to get from diet). Some not produced in body.
Mechanism of action of steroids in activation of specific gene transcription
Steroid Hormone receptors bound to inhibitor until bound by steroid. Binds to SRE simple sequence to DNA, bound to histones, signals RNA pol2. Lipid soluble, carried by proteins until presented to membrane.
3 components/functions of steroid receptor
1. bind ligand, 2. bind DNA, 3. activatees RNA pol2 transcription
Location of functional regions in steroid receptor gene
A/B (N-terminus), C (DNA binding domain), D (hinge), E (C-terminus), F (ligand binding domain (200-400AA, box structure formed from agonist).
Sources of retinoic acids
Lycopene and beta-carotene
Nuclear receptors which hetero-dimerize with RXR
Need RXR as dimer but not functional part. RAR (retinoic acid receptor), VDR (vitD), TR (thyroid), PPAR (paroxisome proliferator activated receptors-big family of alpha, beta, gamma, important in diabetes). RXR homodimer (only homodimer case, doesn't need a ligand to work).
What is the receptor made up of?
2 response elements, 2 DNA-binding domain proteins, 2 ligand binding domains
How does DNA relax for transcription?
Acetylated lysine-->positive charge of histone becomes neutral
Interaction of nuclear receptors with hormone, coactivators, corepressors
1. Inactive receptor: no ligand, no DNA binding, only binding of inhibitory protein permitted. 2. Active receptor: full activation, H12 closes box and ligand, binding permits coactivation. 3. 11 helices, H12 closes with ligand
2 major classes of cancers responding to estrogen and progesterone receptors
1. Responds well to estrogen activity. High chance of regression. No reason to treat with anything else. Mild. Estrogen inhibitors yield excellent results. Need to be active not just present. 2. Estrogen independent-breast tissue used to be responsive to estrogen but no longer is-can grow by own GF w/o estrogen-dangerous. Won't regress with estrogen inhibitor. Estrogen can't work without estrogen receptors.
Used for lack of other options of other antiestrogens. Long term use increases uterine cancer x2.5 but reduces bone fractures by 19%. Reduces risk of developing ER-positive breast cancer but no change in ER-negative breast cancer.
What are glucocorticoids used to treat?
Rheumatoid arthritis, asthma, allograft refection, allergic skin diseases, autoimmune diseases (Lupus).
Transcription factors shown to be crucial for induction of genes ivolved in inflammation
Activator protein (AP)1, nuclear factor (NF)-kB-heterodimer built by p50 and p65
THIS SET IS OFTEN IN FOLDERS WITH...
Intro to endo
YOU MIGHT ALSO LIKE...
B3 Ca Immuno
Medical Interventions Unit 3.2 Review
PHARM: Cancer Chemotherapy MOA, Adverse Effects, a…
MI unit 3
OTHER SETS BY THIS CREATOR
Thyroid- Iodine Def, nodules, displasia