2 min readResearchers Discover Key Protein in Endometrial Cancer Growth

Salt Lake City, UT — The hormone oestrogen plays many critical roles in men and women, in both healthy tissues and in cancer. In breast and gynecologic cancers, oestrogen sends signals to tumours instructing the cancer cells to grow out of control. In recent years, studies have shed light on the growth-promoting role of oestrogen in breast cancer. In endometrial cancer, which arises in the lining of the uterus, oestrogen is known to play a critical role in tumour development, yet many insights from how it affects breast cancer do not apply to endometrial cancer. New research, published today in the journal Cancer Research, outlines findings scientists hope will advance our understanding of endometrial cancer and lead to more effective treatments.

“We started out with a question of how oestrogen signalling works in endometrial cancer,” said Adriana Rodriguez, lead study author. “Most of what we know about oestrogen receptor comes from work in breast cancer, although we know that oestrogen receptor affects different genes in the two cancer types. In this study, we went looking for which proteins influence oestrogen receptor in endometrial cancer cells.” Rodriguez is a PhD student at the University of Utah and is a member of the Jay Gertz Laboratory at Huntsman Cancer Institute (HCI) at the University of Utah (U of U).

The researchers discovered that a protein called ETV4 plays a key role in how oestrogen communicates with endometrial cancer cells. Oestrogen sends pro-growth signals to the cells, and oestrogen receptor carries out these signals. The study found that when ETV4 was removed from endometrial cancer cells, oestrogen signalling was greatly reduced, subsequently leading to diminished tumour growth. “To our surprise, we found that ETV4 helped to promote oestrogen signalling in two ways: first, it was telling oestrogen receptor where to bind in the genome; and second, it was causing more oestrogen receptor to be active,” said Dr. Jay Gertz, a cancer researcher at HCI and assistant professor of oncological sciences at the U of U. Gertz’s lab led the study. “If we can find out what is causing ETV4 to be active, then we have a chance of reducing growth-promoting oestrogen signalling in uterine tumours.”

Gertz’s lab used state-of-the-art genomics techniques and collaborated with several research teams with different expertise to expand the study. Using tissue from human tumours growing in mice, the team analyzed ETV4 and oestrogen receptor in endometrial cancer.

“Uterine cancer is the most common gynecologic cancer and the fourth most common cancer in Utah women,” says Gertz. “Unfortunately, this cancer is on the rise and there are limited treatments for the disease. We believe this study lays the groundwork for future research into ways of blocking oestrogen signalling in endometrial cancer.”

Article adapted from a Huntsman Cancer Institute news release.

Publication: ETV4 Is Necessary for Estrogen Signaling and Growth in Endometrial Cancer Cells. Adriana C. Rodriguez et al. Cancer Research (2020): Click here to view.

endometrial cancer, ETV4 protein, oestrogen

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