Selective oestrogen receptor antagonists inhibit oesophageal cancer cell proliferation in vitro

Al‐Khyatt, Waleed; Tufarelli, Cristina; Khan, Raheela; Iftikhar, S. Y.

doi:10.1186/s12885-018-4030-5

Cited by 25 publications

(26 citation statements)

References 51 publications

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“…Previous research into sex hormone receptor expression in EAC has been sparse and contradictory (see Table 4 ). Similar to our study, earlier studies have identified positive ERβ expression [ 24 – 26 , 28 ] and none or limited ERα expression [ 24 , 25 ] in EAC. Additionally, in a small study of 33 patients, Liu et al .…”

Section: Discussionsupporting

confidence: 92%

“…Clinical studies have shown complex patterns of ER expression in EAC specifically but few studies have been conducted and to date they have been small in size (e.g. 11–28 cases) [ 24 – 28 ]. Similarly, few studies have investigated AR expression in EAC tissue [ 27 , 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, few studies have investigated AR expression in EAC tissue [ 27 , 29 , 30 ]. The association between sex hormone receptor expression and EAC prognosis has also received little attention; one study reported an inverse association between ERβ expression and cancer-specific survival [ 24 ] while another observed no association between AR expression and overall survival [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

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Sex hormone receptor expression and survival in esophageal adenocarcinoma: a prospective cohort study

et al. 2018

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IntroductionA striking epidemiological feature of esophageal adenocarcinoma (EAC) is its strong, unexplained male predominance but few studies have evaluated the prevalence of sex hormone receptor expression in EAC.ResultsA low proportion of EAC tumors stained positive for ERα (4%) and AR (3%) while approximately one third stained positive for ERβ (31%). After a mean follow-up of 3 years (max 9 years), no significant associations were seen for ERα, ERβ or AR expression and EAC recurrence or survival. A non-significant reduction in mortality was observed for positive ERβ tumor expression, when restricting to patients with gastro-esophageal junctional (GEJ) cancer (HR 0.58, 95% CI 0.33, 1.03, p = 0.06).Materials and MethodsWe identified all EAC patients who underwent neo-adjuvant chemotherapy prior to surgical resection between 2004–2012 in the Northern Ireland Cancer Centre. Immunohistochemical expression of ERα, ERβ and AR was scored on triplicate cores to generate H-scores. Cox proportional hazards regression was used to evaluate the association between sex hormone receptor expression and overall, cancer-specific and recurrence-free survival.ConclusionWe found little evidence of ERα or AR expression in EAC. A moderate proportion expressed ERβ and there was suggestive evidence that its expression was associated with improved survival in GEJ cancer patients.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sex hormone receptor expression and survival in esophageal adenocarcinoma: a prospective cohort study

et al. 2018

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“…It is important to note the limitations of the current study, where the role of estrogen receptor was not investigated. Al-Khyatt et al [50] elegantly demonstrated that ERβ was the predominant form in both normal mucosa and esophageal cancer cells, whereas ERα was detected at a minimal level. In addition, these authors showed that the proliferation of OE33 and OE19 cell lines was does-dependently inhibited, while apoptosis was induced by an ERα-specific antagonist (MPP) and an ERβ-specific antagonist (PHTPP), establishing ESR1 and ESR2 as potential therapeutic targets for esophageal adenocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

Disruption of Cancer Metabolic SREBP1/miR-142-5p Suppresses Epithelial–Mesenchymal Transition and Stemness in Esophageal Carcinoma

Huang

Hsu

et al. 2019

Cells

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Elevated activity of sterol regulatory element-binding protein 1 (SREBP1) has been implicated in the tumorigenesis of different cancer types. However, the functional roles of SREBP1 in esophageal cancer are not well appreciated. Here, we aimed to investigate the therapeutic potential of SREBP1 and associated signaling in esophageal cancer. Our initial bioinformatics analyses showed that SREBP1 expression was overexpressed in esophageal tumors and correlated with a significantly lower overall survival rate in patients. Additionally, tumor suppressor miR-142-5p was predicted to target SREBP1/ZEB1 and a lower miR-142-5p was correlated with poor prognosis. We then performed in vitro experiments and showed that overexpressing SREBP1 in OE33 cell line led to increased abilities of colony formation, migration, and invasion; the opposite was observed in SREBP1-silenced OE21cells and SREBP1-silencing was accompanied by the reduced mesenchymal markers, including vimentin (Vim) and ZEB1, while E-cadherin and tumor suppressor miR-142-5p were increased. Subsequently, we first demonstrated that both SREBP1 and ZEB1 were potential targets of miR-142-5p, followed by the examination of the regulatory circuit of miR-142-5p and SREBP1/ZEB1. We observed that increased miR-142-5p level led to the reduced tumorigenic properties, such as migration and tumor sphere formation, and both observations were accompanied by the reduction of ZEB1 and SREBP1, and increase of E-cadherin. We then explored the potential therapeutic agent targeting SREBP1-associated signaling by testing fatostatin (4-hydroxytamoxifen, an active metabolite of tamoxifen). We found that fatostatin suppressed the cell viability of OE21 and OE33 cells and tumor spheres. Interestingly, fatostatin treatment reduced CD133+ population in both OE21 and OE33 cells in concert of increased miR-142-5p level. Finally, we evaluated the efficacy of fatostatin using a xenograft mouse model. Mice treated with fatostatin showed a significantly lower tumor burden and better survival rate as compared to their control counterparts. The treatment of fatostatin resulted in the reduced staining of SREBP1, ZEB1, and Vim, while E-cadherin and miR-142-5p were increased. In summary, we showed that increased SREBP1 and reduced miR-142-5p were associated with increased tumorigenic properties of esophageal cancer cells and poor prognosis. Cells 2020, 9, 7 2 of 15Preclinical tests showed that suppression of SREBP1 using fatostatin led to the reduced malignant phenotype of esophageal cancer via the reduction of EMT markers and increased tumor suppressor, miR-142-5p. Further investigation is warranted for the clinical use of fatostatin for the treatment of esophageal malignancy.

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“…It was found that hormones and their ratios can be used as markers of granulosa cell apoptosis or follicular atresia (Yu et al, ) and an accelerated effect of E‐stimulated granulosa cell apoptosis. Hormone levels were regarded to be connected with cell proliferation and cell apoptosis (Al‐Khyatt, Tufarelli, Khan, & Iftikhar, ; Wang et al, ).…”

Section: Discussionmentioning

confidence: 99%

The effects of phospholipase C on oestradiol and progesterone secretion in porcine granulosa cells cultured in vitro

Chen

Yang

Wang

et al. 2019

Reprod Domestic Animals

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Granulosa cells play important roles in the regulation of ovarian functions. Phospholipase C is crucial in several signalling pathways and could participate in the molecular mechanisms of cell proliferation, differentiation and ageing. The objective of this study was to identify the effects of phospholipase C on the steroidogenesis of oestradiol and progesterone in porcine granulosa cells cultured in vitro. Inhibitor U73122 or activator m‐3M3FBS of phospholipase C was added to the in vitro medium of porcine granulosa cells, respectively. The secretion of oestradiol decreased after 2 hr, 8 hr, 12 hr, 24 hr and 48 hr of treatment with 500 nM U73122 (p < .05) and decreased after 2 hr of treatment in the 500 nM m‐3M3FBS addition group (p < .05). The secretion of progesterone increased after 4 hr of treatment with 500 nM U73122 (p < .05) and increased after 2 hr and 8 hr of treatment in the 500 nM m‐3M3FBS addition group (p < .05). The ratio of oestradiol to progesterone decreased at each time point, except 8 hr after the addition of 500 nM U73122 (p < .05). The ratio of oestradiol to progesterone decreased after 2 hr (p < .05) of treatment with 500 nM m‐3M3FBS. In genes that regulate the synthesis of oestradiol or progesterone, the mRNA expression of CYP11A1 was markedly increased (p < .05), and the mRNA expression of other genes did not change significantly in the U73122 treatment group, while the addition of m‐3M3FBS did not change those genes significantly despite the contrary trend. Our results demonstrated that phospholipase C can be a potential target to stimulate the secretion of oestradiol and suppress progesterone secretion in porcine granulosa cells cultured in vitro, which shed light on a novel biological function of phospholipase C in porcine granulosa cells.

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Selective oestrogen receptor antagonists inhibit oesophageal cancer cell proliferation in vitro

Cited by 25 publications

References 51 publications

Sex hormone receptor expression and survival in esophageal adenocarcinoma: a prospective cohort study

Sex hormone receptor expression and survival in esophageal adenocarcinoma: a prospective cohort study

Disruption of Cancer Metabolic SREBP1/miR-142-5p Suppresses Epithelial–Mesenchymal Transition and Stemness in Esophageal Carcinoma

The effects of phospholipase C on oestradiol and progesterone secretion in porcine granulosa cells cultured in vitro

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