Biological functions and clinical implications of oestrogen receptors alfa and beta in epithelial tissues

Morani, Andrea; Warner, Margaret; Gustafsson, Jan‐Åke

doi:10.1111/j.1365-2796.2008.01976.x

Cited by 115 publications

(104 citation statements)

References 116 publications

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“…Estrogens are known to mediate their diverse functions through two specific intracellular receptors, estogen receptor (ER)-alpha and -beta [3]. Estrogen receptors occur in about two-thirds of breast tumors, and the presence of ER seems to be an important prognostic factor in breast cancer [4].…”

Section: Introductionmentioning

confidence: 99%

SAHA/TRAIL combination induces detachment and anoikis of MDA-MB231 and MCF-7 breast cancer cells

et al. 2012

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a b s t r a c t SAHA, an inhibitor of histone deacetylase activity, has been shown to sensitize tumor cells to apoptosis induced by TRAIL, a member of TNF-family. In this paper we investigated the effect of SAHA/TRAIL combination in two breast cancer cell lines, the ERaÀpositive MCF-7 and the ERaÀnegative MDA-MB231. Treatment of MDA-MB231 and MCF-7 cells with SAHA in combination with TRAIL caused detachment of cells followed by anoikis, a form of apoptosis which occurs after cell detachment, while treatment with SAHA or TRAIL alone did not produce these effects. The effects were more evident in MDA-MB231 cells, which were chosen for ascertaining the mechanism of SAHA/TRAIL action. Our results show that SAHA decreased the level of c-FLIP, thus favouring the interaction of TRAIL with the specific death receptors DR4 and DR5 and the consequent activation of caspase-8. These effects increased when the cells were treated with SAHA/TRAIL combination. Because z-IEDT-fmk, an inhibitor of caspase-8, prevented both the cleavage of the focal adhesion-kinase FAK and cell detachment, we suggest that activation of caspase-8 can be responsible for both the decrement of FAK and the consequent cell detachment. In addition, treatment with SAHA/TRAIL combination caused dissipation of DJ m , activation of caspase-3 and decrement of both phospho-EGFR and phospho-ERK1/2, a kinase which is involved in the phosphorylation of BimEL. Therefore, co-treatment also induced decrement of phospho-BimEL and a concomitant increase in the dephosphorylated form of BimEL, which plays an important role in the induction of anoikis.Our findings suggest the potential application of SAHA in combination with TRAIL in clinical trials for breast cancer.

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Section: Introductionmentioning

confidence: 99%

SAHA/TRAIL combination induces detachment and anoikis of MDA-MB231 and MCF-7 breast cancer cells

et al. 2012

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“…The estrogenic effect was then quantitatively evaluated by the level of expression of the reporter gene encoding the β-galactosidase enzyme (24). Since hER exists in two subtypes, hERα and hERβ (25), distributed within specific tissues, the YES system comprised of human transcriptional intermediary factor 2 (hTIF2) and human steroid receptor coactivator 1 (hSRC1), which exhibited the greatest effectiveness on hERs in the presence of 17β-estradiol (25,26) and flanked by hERα and hERβ, was used in the present investigation.…”

Section: Introductionmentioning

confidence: 99%

Differential binding with ERα and ERβ of the phytoestrogen-rich plant Pueraria mirifica

Boonchird

Mahapanichkul

Cherdshewasart

2010

Braz J Med Biol Res

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“…Thus, to elucidate the whole picture of ERβ action in endometrial cancer, we decided to examine expression of all relevant ERβ transcript variants. Estrogen receptor β previously has been suggested to act as a tumor suppressor in endocrine responsive tissues like the breast and prostate (14)(15)(16). This hypothesis primarily arose from the observed decline of ERβ expression in cancer tissue and from in vitro data demonstrating a growth-inhibitory action of this receptor (17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2012

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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.

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Biological functions and clinical implications of oestrogen receptors alfa and beta in epithelial tissues

Cited by 115 publications

References 116 publications

SAHA/TRAIL combination induces detachment and anoikis of MDA-MB231 and MCF-7 breast cancer cells

SAHA/TRAIL combination induces detachment and anoikis of MDA-MB231 and MCF-7 breast cancer cells

Differential binding with ERα and ERβ of the phytoestrogen-rich plant Pueraria mirifica

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

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