Estrogen interferes with immune surveillance in breast cancer

In a study published online this week in Oncogene, the researchers report that estrogen induces the expression of an inhibitor that blocks immune cells’ ability to kill tumor cells. This is the first study to identify estrogen’s role in shielding breast cancer cells from the action of immune cells.

The researchers analyzed estrogen’s role in the cascade of events that occurs when immune cells, called natural killer cells, encounter a tumor cell. Under normal conditions, natural killer cells release granules that contain enzymes, called granzymes, which enter and kill the tumor cell.

The research team found that when estrogen binds to an estrogen receptor the complex promotes production of a granzyme inhibitor, proteinase inhibitor 9 (PI-9). The inhibitor binds the granzyme, preventing it from initiating the molecular cascade that kills tumor cells.

“It wasn’t known that estrogen could do this in breast cancer cells,” said principal investigator David J. Shapiro, a professor of biochemistry in the School of Molecular and Cellular Biology. “The amounts of estrogen required to do this are quite small.”

U. of I. graduate student Xinguo Jiang also found that when breast cancer cells that contain very high levels of estrogen receptor protein are exposed to low levels of estrogen, they produce large quantities of the granzyme inhibitor and become highly resistant to immune attack.

The researchers were able to show that estrogen’s effect on PI-9 production was the sole mechanism by which estrogen interfered with the natural killer cells’ ability to kill off breast cancer cells. They did so by blocking PI-9 production in the breast cancer cells exposed to estrogen. When these breast cancer cells were targeted by natural killer cells, they were efficiently killed off, even when significant levels of estrogen and estrogen receptor were present.

Estrogens are known to cause only a few types of cancers, Shapiro said. PI-9 also has been implicated in other cancers. High levels of PI-9 in some lymphomas, for example, are associated with poor prognoses.

This study demonstrates how basic research can have important and unanticipated implications for understanding diseases such as breast cancer, Shapiro said. The finding that estrogens stimulate PI-9 production could eventually help drug designers develop new tests – and targets – for breast cancer therapy.

The research team included collaborators from the University of Wisconsin at Madison.

Editor’s note: To reach David J. Shapiro, call 217-333-1788; e-mail: djshapir@uiuc.edu.

Media Contact

Diana Yates University of Illinois

Weitere Informationen:

http://www.uiuc.edu

Alle Nachrichten aus der Kategorie: Life Sciences

Articles and reports from the Life Sciences area deal with applied and basic research into modern biology, chemistry and human medicine.

Valuable information can be found on a range of life sciences fields including bacteriology, biochemistry, bionics, bioinformatics, biophysics, biotechnology, genetics, geobotany, human biology, marine biology, microbiology, molecular biology, cellular biology, zoology, bioinorganic chemistry, microchemistry and environmental chemistry.

Zurück zur Startseite

Kommentare (0)

Schreib Kommentar

Neueste Beiträge

Climate change drives plants to extinction in the Black Forest in Germany

Climate change is leaving its mark on the bog complexes of the German Black Forest. Due to rising temperatures and longer dry periods, two plant species have already gone extinct…

The paradox of quantum forces in nanodevices

Researchers proposed a new approach to describe the interaction of metals with electromagnetic fluctuations (i.e., with random bursts of electric and magnetic fields). Researchers from Peter the Great St.Petersburg Polytechnic…

Seasonal Forecasts Improve Food Supply

EU project CONFER started – precipitation forecasts reduce the impacts of droughts and floods in East Africa. Developing more precise seasonal forecasts to improve food supply for a total of…

By continuing to use the site, you agree to the use of cookies. more information

The cookie settings on this website are set to "allow cookies" to give you the best browsing experience possible. If you continue to use this website without changing your cookie settings or you click "Accept" below then you are consenting to this.

Close