Ovarian cancer sheds tumor suppression with loss of estrogen receptor

An important receptor for estrogen in ovarian cells has been shown to suppress tumor growth, according to a new study published in the August 15 issue of the journal Cancer Research. When ovarian tumors develop, however, the number of these receptors–known as estrogen receptor beta (ER beta)–diminishes, encouraging these tumors to advance toward malignancy and metastasis. This disappearing act may help explain why ovarian cancers are often typically resistant to anti-estrogen drugs including Tamoxifen.

“Ovarian cancer is remarkably lacking in response to antiestrogens such as Tamoxifen,” Gwendal Lazennec, Ph.D., research group leader in molecular and cellular endocrinology of cancers at Inserm U540, Montpellier, France. “We hypothesized that this may be due to the selective decrease that we observed in the expression of message for ER beta in tumors from ovarian cancer patients.”

Tumors from 58 ovarian cancer patients contained less messenger RNA for the ER beta than found in ovarian samples from healthy patients, said Lazennec, whose team included scientists from France and Italy. To understand how the loss of ER beta affected the ovarian cells during cancer progression, the gene for ER beta was replaced in ovarian cancer cell lines that no longer expressed the estrogen-triggered nuclear receptor. The ER beta reintroduced into the cancer cell lines did not share the classic functions attributed to estrogen receptors, including induction of progesterone receptor expression and fibuline-1C, and it’s ability to decrease the expression of the cyclin D1 gene was completely opposite of it’s counterpart, ER beta.

Furthermore, the restored ER beta induced apoptosis, or cell death, in the ovarian cancer cells.

“ER beta appears to have important regulatory functions in the control of the proliferation and motility of ovarian cancer,” Lazennec said. “With the loss of ER beta in ovarian cells, ovarian cancers shed the restrictive properties of this steroid receptor in the regulation of cell growth, death and motility. The loss of ER beta expression appears to be an important event leading to the development of ovarian cancer.”

Lazennec was joined in the ER beta studies by Aurélie Bardin, Pascale Hoffman, Françoise Vignon, Pascal Pujol, from the Unité INSERM 540, as well as Nathalie Boulle, Laboratoire de Biologie Cellulaire et Hormonale, H?pital Arnaud de Villeneuve, and Dionyssios Kasaros, Department of Obstetrics and Gynecology, via Ventimiglia, Turin, Italy.