Estrogen Interferes With Immune Surveillance In Breast Cancer

[Guest guest]

Estrogen Interferes With Immune Surveillance In Breast Cancer

http://www.sciencedaily.com/releases/2007/01/070124115404.htm

Science Daily ­ Estrogen is known to enhance the growth and migration of breast

cancer cells. Now researchers at the University of Illinois at Urbana-Champaign

have found that estrogen also can shield breast cancer cells from immune cells.

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 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.

Note: This story has been adapted from a news release issued by University Of

Illinois At Urbana-Champaign.

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