Effects of steroid hormone therapy on primarily xenotransplanted human colorectal adenocarcinomas

Izbicki, J. R.; Schmitz, R.; Hoppen, H. O.; Izbicki, W.; Troidl, H.

doi:10.1007/bf00390470

Cited by 17 publications

(5 citation statements)

References 24 publications

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“…In cell lines originating from Barrett's esophagus, decreased proliferation in response to the ER ligands was also detected. These findings have not been identified in esophageal adenocarcinoma or Barrett's esophagus cells before, although similar estrogen‐induced pro‐apoptotic phenomena have been reported in other malignancies including colorectal and gastric tumors and in squamous esophageal carcinoma cells KSE‐1 . This is consistent with previously demonstrated changes in specific transcriptional cascades initiated by ER nuclear complexes …”

Section: Discussionsupporting

confidence: 91%

Effect of estrogen on growth and apoptosis in esophageal adenocarcinoma cells

et al. 2012

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The epidemiology of esophageal adenocarcinoma demonstrates a strong gender bias with a sex ratio of 8-9:1 in favor of males. A potential explanation for this is that estrogen might protect against esophageal adenocarcinoma. Estrogen has previously been shown to stimulate apoptosis in esophageal squamous cancer cells. However, the effect of estrogen on esophageal adenocarcinoma cells has not been determined. We used immunoblotting analysis to determine the expression of estrogen receptors, cell adhesion marker E-cadherin, and proliferation marker Ki-67 in cell lines derived from esophageal adenocarcinoma (OE-19, OE-33) and Barrett's esophagus (QhTRT, ChTRT, GihTRT). Estrogen and selective estrogen receptor modulator (SERM)-dependent effects on cell growth were determined by the CellTiter-96 Aqueous Proliferation Assay. Apoptosis was determined by Annexin V/Propidium Iodide cell labeling and flow cytometry. We detected that physiological and supra-physiological concentrations of 17β-estradiol and SERM decreased cell growth in esophageal adenocarcinoma cells. In Barrett's esophagus cells (QhTRT, ChTRT), decreased growth was also detected in response to estrogen/SERM. The level of estrogen receptor expression in the cell lines correlated with the level of anti-growth effects induced by the receptor agonists. Flow cytometry analysis confirmed estrogen/SERM stimulated apoptosis in esophageal adenocarcinoma cells. Estrogen/SERM treatments were associated with a decrease in the expression of Ki-67 and an increase in E-cadherin expression in esophageal adenocarcinoma cells. This study suggests that esophageal adenocarcinoma and Barrett's esophagus cells respond to treatment with selective estrogen receptor ligands, resulting in decreased cell growth and apoptosis. Further research to explore potential therapeutic applications is warranted.

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Section: Discussionsupporting

confidence: 91%

Effect of estrogen on growth and apoptosis in esophageal adenocarcinoma cells

et al. 2012

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“…Moreover, administration of androgens has been linked to the promotion of colon cancer tumorigenesis in rats [22]. On the other hand, steroid hormones induced tumor growth remission in xenotransplanted adenocarcinomas in nude mice [23], arguing for a more complex role of steroid hormones in colon cancer. Since the membrane androgen receptor, in contrast to the classical intracellular androgen receptor, induces tumor regression in target tissues (reviewed in [17]), we sought to determine the expression and functional status of mAR in colon cancer.…”

Section: Introductionmentioning

confidence: 99%

Functional membrane androgen receptors in colon tumors trigger pro-apoptotic responses in vitro and reduce drastically tumor incidence in vivo

Papadopoulou

Gehring

et al. 2009

Mol Cancer

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BackgroundMembrane androgen receptors (mAR) have been implicated in the regulation of cell growth, motility and apoptosis in prostate and breast cancer. Here we analyzed mAR expression and function in colon cancer.ResultsUsing fluorescent mAR ligands we showed specific membrane staining in colon cell lines and mouse xenograft tumor tissues, while membrane staining was undetectable in healthy mouse colon tissues and non-transformed intestinal cells. Saturation/displacement assays revealed time- and concentration-dependent specific binding for testosterone with a KD of 2.9 nM. Stimulation of colon mAR by testosterone albumin conjugates induced rapid cytoskeleton reorganization and apoptotic responses, even in the presence of anti-androgens. The actin cytoskeleton drug cytochalasin B effectively inhibited the pro-apoptotic responses and caspase-3 activation. Interestingly, in vivo studies revealed that mAR activation resulted in a 65% reduction of tumor incidence in chemically induced Balb/c mice colon tumors.ConclusionOur results demonstrate for the first time that functional mARs are predominantly expressed in colon tumors and that their activation results in induction of anti-tumor responses in vitro and extensive reduction of tumor incidence in vivo.

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“…Within the minority of patients whose tumors expressed ERα and AR, the majority of expression was also detected in male EAC patients. Preclinical data have shown that estrogen and selective estrogen receptor modulator treatment decreases tumor growth, proliferation and increase apoptosis in EAC and Barrett's esophagus cell lines [ 13 , 14 ] and similar effects have been reported in vitro and in vivo for gastric [ 31 , 32 ] and colorectal cancer [ 33 ] and esophageal squamous cell carcinoma (OSSC) [ 20 , 34 ]. Interestingly, ERβ has been correlated with improved survival in non-small cell lung adenocarcinoma, particularly in men [ 35 ], although findings from other studies have been mixed [ 36 , 37 ] and a recent pooled analyses found no association between ERβ expression and survival in NSCLC patients [ 38 ].…”

Section: Discussionmentioning

confidence: 76%

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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Effects of steroid hormone therapy on primarily xenotransplanted human colorectal adenocarcinomas

Cited by 17 publications

References 24 publications

Effect of estrogen on growth and apoptosis in esophageal adenocarcinoma cells

Effect of estrogen on growth and apoptosis in esophageal adenocarcinoma cells

Functional membrane androgen receptors in colon tumors trigger pro-apoptotic responses in vitro and reduce drastically tumor incidence in vivo

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

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