Abstract 501: Effect of estrogen receptor beta isoforms on the function of estrogen receptor beta in estrogen recpetor alpha negative breast cancer cell lines.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC African American (AA) women with breast cancer are more likely to be diagnosed at a more advanced stage of the disease, have a higher recurrence rate and a poorer prognosis than Caucasian (CA) women. African American women are more often diagnosed with high-grade breast tumors at an earlier age (pre-menopausal), most of which are negative for the estrogen and progesterone receptors (ER-, PR-). These factors result in a higher mortality rate among AA breast cancer patients. This survival disparity can be attributed to socioeconomic status and other related factors, however, there are biological factors that may also be involved. The insulin-like growth factor II (IGF-II) plays a crucial role in fetal and cancer development by signaling through the IGF-I receptor (IGF-IR), the insulin receptor (Ins-R) and also crosstalk with the estrogen receptor alpha (ER-α). Compared to CA women, AA women have an increased level of proIGF-II expression in breast tissues and higher signaling activation through the IGF-1 and Ins-R. Studies have shown that the estrogen receptor beta (ER-β) is also expressed in a majority of breast cancers. The estrogen receptor (ER) as well as the progesterone receptor and Her2Neu have been the most common markers used for determining breast cancer status. Most research done in breast cancer as it pertains to the ER status has mainly been done in cells and tissues expressing the Estrogen Receptor Alpha (ER-α). However, with its discovery in 1996, the Estrogen Receptor Beta (ER-s) has lead to a better understanding the breast cancer disease. Studies have shown that the estrogen receptor beta (β) is expressed in a majority of breast cancers, including cancers designated as ER negative (ER-). The tumor suppressing function of ER-β has been described based on its interaction with ER-α, however it's function in the absence of ER-α has not been clearly assessed. ER-β has 5 isoforms of which ER-β isoform 5 (ER-β5) is the most abundantly expressed among AA women with triple negative breast cancer. ER-β5 expression is associated with a poor prognosis and decreased survival of breast cancer patients. Therefore, we hypothesize that the heterodimerization and subsequent activation of ER-β with its isoforms, mainly ER-β5, leads to a suppression of its function in breast cancers not expressing ER-α, thus preventing cell death. To test this hypothesis we analyzed the basal expression of ER-β and all of its isoforms (ER- β1-5) in AA and CA normal and breast cancer cell lines. The expression of ER-β5 increased in cells lines in response to insulin like growth factor-II (IGF-II). IGF-II promotes the phosphorylation of ER-β and ER-β5 and may regulate the ER-β signaling pathway in ER-α negative cell lines. Citation Format: Chane’ N. O'Bannon. Effect of estrogen receptor beta isoforms on the function of estrogen receptor beta in estrogen recpetor alpha negative breast cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 501. doi:10.1158/1538-7445.AM2013-501