Coactivator stokes continuing fire of endometriosis

(Medical Xpress) -- Endometriosis, which can cause severe pain and even infertility in the estimated 8.5 million U.S. women it affects, is driven by one of the cell's master regulators ­ steroid receptor coactivator 1 or SRC-1, said researchers at Baylor College of Medicine in a report that appears online today in the journal Nature Medicine.

"This finding could lead to new therapies for this age-old condition," said Dr. Bert O'Malley, chair of molecular and cellular biology at BCM and the report's corresponding author.

The causes of are unclear, because the molecular pathways involved have not been elucidated previously. The disorder involves the abnormal growth of cells similar to those of the lining of the uterus (the endometrium) outside that organ ­ on the ovaries, fallopian tubes, pelvic cavity lining or other structures.

No one knows for sure how the endometrial tissue travels from the uterus to other structures but most believe that the tissue could back up into the abdomen through the fallopian tubes during a woman's monthly period. Estrogen can promote the growth of endometriosis.

Immortalized cells

Although the cells of endometriosis are not cancerous, they can become "immortalized," growing and reproducing and invading normal tissues. In studies in mice and human tissue, O'Malley and his colleagues identified a truncated form of SRC-1 in endometrial cells.

This coactivator fragment cooperates with two other proteins known to play a role in endometriosis ­ TNF-alpha (tumor necrosis factor alpha) and MMP9 (matrix metallopeptidase 9) ­ to keep the endometrial cells alive and growing.

"Although the full SRC-1 molecule will actually increase the death of endometriosis cells, the full coactivator gets processed by the inflammatory process into a smaller piece (an isoform) that stops the from dying," said O'Malley. "We now know the mechanism that causes this to happen."

SRC-1 isoform

Understanding the role of the isoform of SRC-1 in maintaining the endometriosis is an important step toward developing new ways to treat it, said O'Malley.

Others who took part in this work include a lead coauthor, Dr. Sang Jun Han, and Drs. Shannon M. Hawkins, Khurshida Begum, Sung Yun Jung, Ertug Kovanci, Jun Qin, John P. Lydon, Francesco J. DeMayo, all of BCM.

More information: DOI: 10.1038/nm.2826

Related Stories

Master gene SRC-3 enables breast cancer growth, invasion

Feb 12, 2010

The master gene called SRC-3 (steroid receptor coactivator 3) not only enhances estrogen-dependent growth of cancer cells by activating and encouraging the transcription of a genetic message into a protein, it also sends ...

Deactivating a cancer growth promoter

Sep 25, 2008

Three enzymes called phosphatases that shut down a molecule called SRC-3 (steroid receptor coactivator 3) could provide a new pathway for fighting cancer, particularly tumors of the breast and prostate, said researchers at ...

Scientists identify possible cause of endometriosis

Aug 05, 2008

Endometriosis is a condition whereby patches of the inner lining of the womb appear in parts of the body other than the womb cavity. It can cause severe pain and affects approximately 15% of women of reproductive ...

Recommended for you

Putting the brakes on cancer

Dec 19, 2014

A study led by the University of Dundee, in collaboration with researchers at our University, has uncovered an important role played by a tumour suppressor gene, helping scientists to better understand how ...

Peanut component linked to cancer spread

Dec 19, 2014

Scientists at the University of Liverpool have found that a component of peanuts could encourage the spread and survival of cancer cells in the body.

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.