Group items tagged

Studies in breast cancer and prostate cancer have revealed different effects by ER alpha vs ER beta.  It is no surprise that the same effects are found in ovarian cancer.  This study found ER alpha antagonists and ER beta agonists "significantly" suppressed growth in the ovarian cancer cell lines SKOV3 and OV2008.  Also, ER alpha agonist and ER beta antagonist "significantly" increased growth in the same cell lines.  These findings point to in increased proliferation with ER alpha and decreased with ER beta.  This is consistent with breast and prostate cancer also.

Very nice study.  The authors looked at normal prostate, early disease and late stage prostate cancer.  The authors found that ER beta expression, as a general rule, was lost as progression occurred to the high-grade dysplasias and grad 4/5 carcinomas of the prostate.  Early low/moderate dysplasia was associated with an increase in ER beta--the authors propose that this was due to an attempt of the basal epithelium to counter the paracrine effect of ER alpha.   In contrast, androgen receptors appeared to be equally expressed across all.

Estrogen receptors alpha and beta show dominance in the proliferative phases, with alpha isoform predominating.  In the secretory phase, less expression of ER was present. ER alpha was predominantly expressed in the epithelial and stromal cells in the proliferative phase.  ER beta was predominantly expressed in glandular cells in the same proliferative phase.   in the luteal phase, ER alpha expression declined in the funtionalis layers.  ER alpha in the basalis remained unchanged.  ER beta in the functionalis layers also declined in the luteal phase.   No relative change was found in the weak expression of ER alpha/beta in the myometrium.

ER-beta inhibits ER-alpha activation of cell proliferation via cyclin D1 gene expression.  This points to ER-beta as a counter regulatory receptor to ER-alpha.  This explains how a loss of ER-beta expression is found to be associated with increased cancers.  

ER-beta expression appears to regulate estrogenic activity through ER-alpha expression.  Co-expression of ER-alpha and ER-beta is associated with reduced estrogenic signaling, indicating a significant counter regulatory role for ER-beta.

ER alpha and ER beta have different effects on the uterus in this mice model.  ER beta modulates ER alpha.  ER beta decreases PR, whereas ER alpha increases PR.

ER beta plays an important role in the prostate.  Loss of ER beta expression in the prostate has been shown to promote carcinogenesis.  In addition, 3-beta androstanediol, a DHT metabolite has been shown to signal through ER beta.

Great article!!  Nice discussion of the complexity of hormones.  Women on aromatase inhibitors can make estrogen from Testosterone.  This is important with estrogen sensitive cancer as in breast cancer.  This will occur via alternative pathways: Testosterone to DHT via 5 alpha reductase and then DHT to 3 beta androstanediol via 3 beta HSD.  3 beta androstanediol is a male hormone metabolite that binds to estrogen receptors.  The affinity is less than Estradiol, but appears to have a higher affinity for ER beta over ER alpha. 

Great article on ER beta and the prostate.  ER alpha expression is very important in the development of the prostate.  IN that instance, ER beta is down regulated.  In prostate cancer generation, ER beta expression in the epithelium is lost.

Increased survival in those with ER beta + and ER alpha -.  Early relapse was associated with lack of ER beta expression.  ER beta is transcribed from a different genomic location than ER alpha.  

ER beta expression and the ratio of ER alpha/ER beta is important in prognosis and effectiveness of SERM therapy like tamoxifen.  This study looked at the aromatase inhibitor anastrazole as well.

Study finds ER-beta plays more significant role in the development of Colon cancer than ER-alpha in women.  HRT in women reduces colon cancer risk in comparison to breast, which is increased.  Shows the different tissue expression of ER-alpha and ER-beta, as well as the HRT itself.

ER-beta found throughout both the proliferative and secretory phases of the menstrual cycle.  ER-beta expression was higher in the proliferative versus the secretory phases, though not statistically significant.  This makes since as estrogen stimulation dominates the proliferative phase.  Additionally, ER-beta expression was found throughout all levels of the endometrium and the myometrium.

Loss of ER beta associated with higher risk of colon cancer.  ER beta has been shown to be highly expressed in health colons.  It has been proposed that loss of this ER beta expression is associated with carcinogenesis.

3-beta androstanediola, a product of 3alpha-HSD from DHT binds to ER beta and down regulates AR in prostate cancer.  This study proposes that the mechanism is via CYP7B1.  CYP7B1 inactivates 3-beta androstanediol.  Interesting, because 3-beta androstanediol is considered "inactive" when compared to 3-alpha androstanediol and its interaction with ER alpha.  

The process of androgen deprivation therapy needs to be re-evaluated.  Why?  First, the CVD side effects associated with the androgen depletion.  Second, the depletion of 3 beta androstanediol that has been shown to bind to ER beta and inhibit growth.  As in this study that finds that ER beta activity slows prostate cancer through destabilizing of HIF-1 alpha and by inhibiting VEGF.

ER beta expression is dominant in healthy colon epithelium.  This study found that as colon disease progressed, ER beta expression declined.  So that, early disease was associated with the highest level of ER beta expression.

Estrogen receptors are primarily located inside the nucleus and in the cytoplasm; not on the cell membrane surface. This article specifically focus' on the non-genomic action of ER-beta.  ER-alpha and ER-beta are classic transcription factors.

ER-beta is commonly expressed versus ER-alpha in bladder cancer.  There was a positive correlation between ER-beta expression and invasion and grade of cancer.  This study also found that blockade of the ER resulted in a decrease in growth.

ER beta and prostate cancer.  More aggressive prostate cancer is found to be associated with lower ER beta expression in the prostate.  this makes sense, as other studies have shown that ER beta in the prostate can induce apoptosis (cell death), which is a powerful mechanism to regulate uncontrolled growth as found in cancer.