Estrogen receptor β transcript variants associate with oncogene expression in endometrial cancer

Abstract

Abstract. The human ESR2 gene codes for estrogen receptor β1 and for multiple splice variants, which are suggested to exert distinct functions in the cellular estrogen response. Given that the function of ERβ in endometrial cancer remains unclear, we examined the expression of ERβ1, ERβ2 and various further ERβ transcript variants and their association with selected cancer-related genes in 74 human endometrium samples and endometrial cancer specimens by means of RT-qPCR. Additionally, we knocked down ERβ expression in HEC-1A endometrial adenocarcinoma cells by means of siRNA transfection. Expression of four ERβ transcript variants was significantly elevated in cancer tissue or in G3 tumors compared to postmenopausal endometrium. Expression of ERβ1, ERβ2, ERβ5 and five further variants was associated with the oncogenes MYBL2 or HER2 in endometrial cancer. In addition, siRNA-triggered knockdown of ERβ expression led to a significant decline of MYBL2 mRNA and protein levels in endometrial cancer cells. Our observation of increased ERβ transcript levels in cancer tissue and particularly their correlation with the expression of oncogenes, as well as the results of our knockdown studies, suggest a role of ERβ in endometrial carcinogenesis.

Dual expression of immunoreactive estrogen receptor β and p53 is a potential predictor of regional lymph node metastasis and postoperative recurrence in endometrial endometrioid carcinoma

“…Although ERβ has been suggested to coordinately play an important role in maintaining the normal function of the endometrium together with ERα, the precise physiological roles of ERβ in endometrial function remain unclear [ 33 ]. Similarly, the possible involvement of ERβ in the carcinogenesis of endometrial carcinoma is still being debated [ 5 , 7 , 34 ]. Recently, an abnormal balance between the two ER subtypes was suggested to be involved in carcinogenesis, tumor invasion, and poor clinical outcomes in patients with gynecologic malignant tumors [ 8 , 35 ].…”

“…Estrogen receptor (ER) α has been reported to play an important role in the development of estrogen-dependent malignant tumors. However, recent studies have proposed that ERβ is also associated with gynecologic malignant tumors [ 5 , 6 ]. Moreover, researchers also demonstrated that the expression of ERβ in endometrial endometrioid carcinoma is greater than that in the normal endometrium [ 5 , 7 ] and that a high ERβ/ERα expression ratio is an independent prognostic marker of survival in patients with endometrial endometrioid carcinoma [ 8 ].…”

“…However, recent studies have proposed that ERβ is also associated with gynecologic malignant tumors [ 5 , 6 ]. Moreover, researchers also demonstrated that the expression of ERβ in endometrial endometrioid carcinoma is greater than that in the normal endometrium [ 5 , 7 ] and that a high ERβ/ERα expression ratio is an independent prognostic marker of survival in patients with endometrial endometrioid carcinoma [ 8 ]. Additionally, human endometriotic cells extracted from patients with endometriosis exhibit higher expression of ERβ than cells extracted from patients without endometriosis [ 9 ].…”

The Estrogen Receptor Joins Other Cancer Biomarkers as a Predictor of Outcome

“…ER- β expression, though lower than ER- α in most endometrial cancers, may be induced in some tumors, in particular endometrial tumors of a higher grade [28]. Reports suggest that it may inhibit the function of ER- α and/or that it may be a marker for poor outcome [29, 30].…”

“…Reports suggest that it may inhibit the function of ER- α and/or that it may be a marker for poor outcome [29, 30]. However, these data are complicated by the presence of several ER- β splice variants that are differentially associated with tumor grade [28]. …”