University of California San Francisco
Helen Diller Family Comprehensive Cancer Center

Study Identifies How Tamoxifen Stimulates Uterine Cell Growth and Cancer

By Kristen Bole, UCSF News Office | July 3, 2009

UCSF researchers have identified a new "feed-forward" pathway linking estrogen receptors in the membrane of the uterus to a process that increases local estrogen levels and promotes cell growth.

The research is significant in helping determine why tamoxifen and other synthetic estrogens are linked to increased rates of endometriosis and uterine cancer, and identifies a pathway that could be targeted in drug therapies for those diseases, researchers say.

Findings are published in the July 1, 2009 issue of "Cancer Research," the journal of the American Association for Cancer Research. The paper also can be found online at http://cancerres.aacrjournals.org/current.shtml.

The research found that when activated by estrogens, endometrial cells obtained from patients suffering from endometriosis or human uterine cancer cells initiate a previously unknown cascade of signals that leads to cellular replication and further estrogen production, the paper says.

The ensuing cycle leads to abnormal growth of the cells lining the uterus, or endometrium, which occurs in endometriosis and uterine cancer, according to senior author Holly A. Ingraham, PhD, a professor in the UCSF School of Medicine's Department of Cellular and Molecular Pharmacology.

"It turns out that displaced endometrial cells, such as those used in this study, are estrogen factories," said Ingraham, who also is affiliated with the UCSF Helen Diller Family Comprehensive Cancer Center and the UCSF Center for Reproductive Sciences. "They pump out estrogen in a feed-forward pathway, so the more estrogen they produce, the more estrogen they're capable of producing."

Read more at Kristen Bole, UCSF News Office