Sex-specific differences in the expression levels of estrogen receptor subtypes in colorectal cancer

Nüssler, Natascha C.; Reinbacher, Katrin; Shanny, Naama; Schirmeier, Anja; Glanemann, Matthias; Neuhaus, P.; Nüssler, Andreas K.; Kirschner, Martin

doi:10.1016/j.genm.2008.07.005

Cited by 59 publications

(46 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Estrogen not only modulates cell proliferation in classic estrogen-sensitive tissues, but also in other tissues such as (19) and stomach (15,16). An epidemiological study showed that tamoxifen, an anti-estrogen agent, may increase the incidence of gastric cancer, which suggested that estrogen may be involved in the pathogenesis of gastric cancer (20).…”

Section: Discussionmentioning

confidence: 99%

Expression of ERα36 in gastric cancer samples and their matched normal tissues

Wang¹,

Fang³

et al. 2011

Oncology Letters

View full text Add to dashboard Cite

Abstract. Estrogen receptor α36 (ERα36) is believed to mediate membrane-initiated effects of estrogen signaling, and promote cell growth and resistance to tamoxifen treatment. However, few studies are available regarding ERα36 expression in gastric cancer. In the present study, we evaluated the expression of ERα36, as well as estrogen receptor α66 (ERα66), in gastric cancer and its correlation with clinicopathological parameters. Real-time polymerase chain reaction (PCR) was applied to detect the expression of ERα66 and ERα36 mRNA in 45 pairs of samples of gastric cancer tissues and matched normal tissues. The ΔΔCT method was used to evaluate the relative quantity of target mRNA expression. Among the 45 pairs of samples of gastric cancer tissues and matched normal tissues adjacent to the tumor, the ERα36 mRNA levels in normal tissues were significantly higher than those observed in gastric cancer tissues (p=0.040). Additionally, the expression of ERα66 mRNA levels between gastric cancer tissues and matched normal tissues had no statistically significant difference. We confirmed that ERα36 mRNA was expressed in the four gastric cancer cell lines, and ERα66 mRNA was expressed in two of the four gastric cancer cell lines. According to the tissue and cell findings, it was suggested that the expression level of ERα36 is greater than that of ERα66 in gastric cancer. In conclusion, the expression of ERα66 and ERα36 in gastric cancer tissues and cells was confirmed in this study. A decreased expression of ERα36 mRNA in gastric cancer tissues may be one of the factors affecting tumorigenesis in gastric cancer patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Expression of ERα36 in gastric cancer samples and their matched normal tissues

Wang¹,

Fang³

et al. 2011

Oncology Letters

View full text Add to dashboard Cite

show abstract

“…The effects on TS expression have been observed for ERß, but only ER· is currently tested in histopathology laboratories (35) to study tumours like breast cancer. The effect of ER· is opposite to the antiproliferative action of ERß (34) and information regarding its expression in CRC is even scarcer than that available for the latter. In addition, gene polymorphisms within ER· gene have been recently associated with the development of microsatellite unstable colorectal tumours and might affect ER expression (36).…”

Section: ------------------------------------------------------------mentioning

confidence: 99%

“…However, previous history of hormone replacement use, that might explain such differences, was unknown. The protective effect of hormone replacement therapy against CRC is well documented (20)(21)(22), but information about hormonal status and/or use of postmenopausal hormone is not always accessible to researchers (34).…”

Section: ------------------------------------------------------------mentioning

confidence: 99%

“…Among them, ERß1 is proposed as the one able to activate oestrogen responsive elements, but little is known about the functional effect of the others. Nüssler et al (34) have recently reported differential expression of ER· and ERß subtypes in normal and tumour mucosa in CRC patients, with significant divergences in men, but not in women. They postulate that gender-specific differences in the pathogenesis of CRC are due to ER·/ERß ratio, rather than to a separate ER subtype, though ERß level directly correlated with the degree of tumour differentiation in male patients.…”

Section: ------------------------------------------------------------mentioning

confidence: 99%

See 1 more Smart Citation

Influence of thymidylate synthase DNA polymorphisms and gender on the clinical evolution of patients with advanced colorectal cancer

Fernández-Contreras¹

2010

Oncol Rep

View full text Add to dashboard Cite

Abstract. Experimental evidence has revealed that several thymidylate synthase (TS) DNA polymorphisms modulate gene expression, which, in turn is known to be downregulated by oestrogen receptor subtypes. Consequently, this process might be influenced by female hormones. Based on these data, we investigated whether patient's gender and TS polymorphism exert an interactive effect on the clinical evolution of patients with advanced colorectal cancer (CRC) subjected to 5 fluorouracil (5FU)-based adjuvant chemotherapy. A retrospective study was carried out on paraffinembedded sections from 81 CRC patients. A variable tandem repeat (VNTR) of 28 bp, a G/C single nucleotide polymorphism (SNP), and a deletion of 6 bp (ins1494del 6 bp) were studied. Genotyping methods were polymerase chain reaction (PCR) for VNTR, and PCR followed by restriction length fragment polymorphism (PCR-RFLP) for SNP and ins1494del 6 bp. The effect of TS genotype and gender on overall and progression-free survival was assessed in univariate and multivariate (Cox regression model) tests. In male patients, the study of combined TS genotypes showed that G&6 + /6 + was an adverse marker for overall (P=0.04; median: not reached) and progression-free survival (P=0.03; median: 12 months, 95% CI: 0-32.4). In the multivariate analysis, the concurrence of G&6 + /6 + combination and male patients resulted in a 5.5-fold increased risk of relapse or disease progression (95% CI: 1-32.1; likelihood test P=0.004; interaction P=0.06). TS genotype did not affect survival among women. The present study supports that the effect of TS polymorphisms on the clinical evolution of advanced CRC patients is significantly influenced by gender.

show abstract

“…Most human colon tumors are characterized by the abundant expression of ERb (21). To add to the complexity, human colon tumors that were screened for ERb expression displayed a remarkable inverse relationship between levels of ERb expression and tumor grading type (22) and a loss of ERb in human colon tumors was observed (23,24). Thus, it is unclear as to what exact role ERb may play during colon carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

Soy Isoflavones Modulate Azoxymethane-Induced Rat Colon Carcinogenesis Exposed Pre- and Postnatally and Inhibit Growth of DLD-1 Human Colon Adenocarcinoma Cells by Increasing the Expression of Estrogen Receptor-β

Raju¹,

Bielecki²,

Caldwell³

et al. 2009

The Journal of Nutrition

View full text Add to dashboard Cite

We studied the effects of lifetime exposure to dietary soy isoflavones in an azoxymethane (AOM)-induced rat colon cancer model. Male pups born to Sprague-Dawley rats exposed (including during pregnancy and lactation) to soy isoflavones at either no (0 mg = control), low (40 mg), or high (1000 mg) doses/kg diet were weaned and continued receiving their respective parental diets until the end of the study. Weaned rats received 2 subcutaneous injections (15 mg/kg body weight) of AOM 1 wk apart. After 26 wk, rats were killed and the coordinates of colon aberrant crypt foci (ACF) and tumors were determined. Expression of estrogen receptor (ER)-beta was assessed in rat colon tumors and in DLD-1 human colon adenocarcinoma cells exposed to soy isoflavones. Compared with the control, soy isoflavones did not affect incidences or multiplicities of colon ACF or tumors. Low-dose soy isoflavones decreased tumor burden and size compared with the control (P < 0.05). Expression of ERbeta increased in colon tumors of soy isoflavone-treated groups compared with the control. Soy isoflavones dose-dependently arrested the growth of DLD-1 cells and at subcytotoxic levels increased the expression of ERbeta. Our results suggest that pre- and postnatal exposure to dietary soy isoflavones suppresses the growth of colon tumors in male rats. The overexpression of ERbeta in both rat colon tumors and DLD-1 cells caused by soy isoflavones suggests that ERbeta is a critical mediator in mitigating its cancer-preventive effects.

show abstract

Sex-specific differences in the expression levels of estrogen receptor subtypes in colorectal cancer

Cited by 59 publications

References 19 publications

Expression of ERα36 in gastric cancer samples and their matched normal tissues

Expression of ERα36 in gastric cancer samples and their matched normal tissues

Influence of thymidylate synthase DNA polymorphisms and gender on the clinical evolution of patients with advanced colorectal cancer

Soy Isoflavones Modulate Azoxymethane-Induced Rat Colon Carcinogenesis Exposed Pre- and Postnatally and Inhibit Growth of DLD-1 Human Colon Adenocarcinoma Cells by Increasing the Expression of Estrogen Receptor-β

Contact Info

Product

Resources

About