Tag Archives: Estrogen receptor

New advances halt expansion of breast cancer stem cells

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Scientists have discovered a novel way to halt the expansion of breast cancer stem cells (CSCs).

Breast cancer stem cells (CSCs), the aggressive cells thought to be resistant to current anti-cancer therapies and which promote metastasis, are stimulated by estrogen via a pathway that mirrors normal stem cell development.

Disrupting the pathway, researchers were able to halt the expansion of breast CSCs, a finding that suggests a new drug therapy target.

“A critical aspect of our work was to discover that estrogen could promote breast cancer growth by modulating the proportion of breast CSCs. Since CSCs were not directly sensitive to estrogen, it wasn”t clear how estrogen could affect their numbers. However, we found that hormone-sensitive cancer cells can communicate with CSCs to regulate their numbers. By disrupting the interaction between cancer cell populations we were able to prevent tumor growth,” said Charlotte Kuperwasser, associate professor in the anatomy and cellular biology and radiation oncology departments at Tufts University School of Medicine, and member of the genetics and cell, molecular and developmental biology program faculties at the Sackler School of Graduate Biomedical Sciences at Tufts.

Breast cancer

Breast cancer

“Interestingly, this signaling pathway involves many of the same players that control normal stem cell biology, raising a more general possibility that CSCs in other tumors might be regulated by the mechanisms guiding normal development,” said Kuperwasser.


Kuperwasser and colleagues from MIT and Harvard used a mouse model to examine the behavior of cancerous human breast tissue with a method that mimics the human body more closely than standard mouse models. The researchers first examined estrogen”s effect on breast CSC growth, finding that estrogen caused breast CSC numbers to increase by nearly 800 percent. Since few breast CSCs contain estrogen receptors, the researchers suspected that estrogen”s actions were through a signaling mechanism from nearby cells that express the receptors.

“When nearby cells were exposed to estrogen, they secreted 14 times more FGF9, a signaling protein that drives CSC proliferation. When we blocked the FGF pathway with a small molecule inhibitor, we saw loss of CSC growth, tumorspheres generation, and even tumor formation. We then linked FGF signaling to the Tbx3 signaling axis, which is also important for embryonic mammary gland development,” said first author Christine Fillmore, PhD, a 2009 graduate of the genetics program at the Sackler School and currently a research fellow in genetics at Children”s Hospital Boston.

“These results show that interfering with this signaling pathway is a promising strategy for targeting breast CSCs. We are hopeful that the improved understanding of the mechanisms that promote breast CSCs will lead to the development of drugs that can be used to halt CSC proliferation,” said Kuperwasser.

The study has been published in the Proceedings of the National Academy of Sciences (PNAS) Early Edition.

Liquorice root could treat neurodegenerative diseases

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A compound found in liquorice root could help prevent or slow down the cell death associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases, says a neuroscientist at the University of South Carolina.

Dr. Rosemarie Booze, the Bicentennial Chair Professor in Behavorial Neuroscience in the university’s College of Arts and Sciences, is isolating liquiritigenin — or LQ, as Booze calls it — and is testing its neural effects.

LQ is a phytoestrogen, a compound that is found naturally in plants and that mimics the hormone estrogen. Phytoestrogens bind to one of two types of estrogen receptors (ER) — alpha and beta — found in cells in the human body, said Booze.

Liquorice root

Liquorice root

Ones that target alpha ERs, which are found throughout the body, have demonstrated qualities that may prevent some cancers, including breast, ovary and uterus. Beta ERs, which LQ targets, are found in cells in the brain.


“Plants are amazing chemists!” Booze said. “Phytoestrogens are only made by plants, and there are several different ones that target estrogen receptors. We are focusing on the beta compounds for neural effects, and these can be found in liquorice root, soybeans and other plants.”

Liquorice root

Liquorice root

“Alpha and beta estrogen receptors are very close in structure, but beta estrogen receptors are more localized in the brain and have different effects on brain cells,” Booze said. “We know that LQ is the active compound in one traditional Chinese medicine and is used to treat post menopausal women. We’re looking at it for its brain effects.”

Alzheimer’s, Parkinson’s and HIV-related dementia are neurodegenerative diseases because they involve the loss of neurons, or brain cells, over time.

“We’re testing the ability of plant-derived phytoestrogens, such as genistein and LQ, to help nerve cells survive in neurodegenerative diseases and keep neurons connected and functional,” she said. “We want to maintain that brain plasticity.”