Expression of estrogen receptors in gastric cancer and their clinical significance

Abstract.The relationship between estrogen receptor (ER)α and patient prognosis has been identified in gastric cancer; however, the definite role of ERα in gastric cancer remains to be fully elucidated. The aim of the present in vitro study was to investigate the impact of ERα on cell proliferation, migration and invasion in gastric cancer cell lines. We investigated the biological effect of ERα overexpression on gastric carcinoma cells. An MKN28 gastric cancer cell line stably overexpressing ERα was established. The effect of ERα overexpression on cell growth was assessed by evaluating cell survival, colony formation, cell cycle progression and apoptosis. Cell migration and invasion were detected by Transwell migration/invasion assays. The protein levels of several potentially involved genes were determined by western blotting to elucidate the underlying molecular mechanisms. The Student's t-test was used to determine the statistical differences between various experimental and control groups, and one-way ANOVA test was used to determine the difference between three or more groups. The results showed that ERα overexpression significantly inhibited cell growth and proliferation, blocked cell entry into the G1/G0 phase and promoted cell apoptosis. In addition, ERα reduced the motility and invasion of gastric cancer cells. These phenotypes may partly be explained by a decrease in β-catenin expression caused by ERα overexpression. ERα overexpression effectively inhibited cell growth and cancer progression by suppressing β-catenin in gastric cancer, identifying ERα as a promising target with therapeutic potential for development of new approaches to treat gastric cancer.

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“…Consistent with our result, several studies also found that ERα cannot be detected in gastric cancer cell lines (46,47).…”

Section: Estrogen Protects Against Gastric Cancer Through Erssupporting

confidence: 93%

Overexpression of ERα inhibits proliferation and invasion of MKN28 gastric cancer cells by suppressing β-catenin

Zhou

Teng

et al. 2013

Oncology Reports

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“…This distribution is not clearly explained by the differences in the prevalence of risk factors between the genders. There have been conflicting reports of the effect of sex hormones on the development of gastric cancer [15,16]. According to a meta-analysis by Camargo et al [15], a longer period of fertility and hormonal replacement therapy were each associated with decreased gastric cancer risk.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological characteristics and prognosis of signet ring cell carcinoma of the stomach

et al. 2013

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Background Signet ring cell carcinoma (SRC) of the stomach is a histological type based on microscopic characteristics. Although the distinctive clinicopathological features of SRC have been reported, results are inconsistent and survival outcomes are uncertain. Methods We retrospectively studied 769 patients with gastric carcinoma who underwent gastrectomy in our institute from 1999 to 2009. Among them, 326 patients (42.4 %) had early gastric cancer (EGC) and 443 patients (57.6 %) had advanced gastric cancer (AGC). Sex, age, tumor location, macroscopic type, tumor size, microscopic invasion, and survival rate were compared between patients with SRC, differentiated-, and undifferentiated-type gastric carcinomas. Results Fifty-one patients (15.6 %) had SRC in EGC; there were significant differences in sex, age, location, macroscopic type, and size between SRC and the differentiated histological type. However, there was no difference between SRC and undifferentiated-type gastric carcinoma, except for the macroscopic type. Fifty-seven patients (12.9 %) had SRC in AGC. Sex, age, location, size, macroscopic type, perineural invasion, N stage, and hepatic metastasis were significantly different between SRC and the differentiated histological type. Undifferentiated-type gastric carcinoma differed in sex, macroscopic type, and hepatic metastasis. The overall survival rate differed between SRC and other cell types (P \ 0.001). Among all the study patients, age [hazard ratio (HR) 1.013, P = 0.041] and tumor, node, and metastasis (TNM) stage (HR 2.350, P \ 0.001) were important factors for predicting survival. Omitting patients with palliative resection or metastases, TNM stage was still an important factor for survival (HR 2.077, P \ 0.001). Conclusions Patients with SRC showed similar clinicopathological features with undifferentiated histology. The survival of patients with SRC reflected a better prognosis in patients with undifferentiated gastric carcinoma. However, when narrowing the patients to those with EGC only, survival in EGC patients exhibited no difference between histological types. Among AGC patients, SRC patients had a worse prognosis than other cell types.

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“…In addition, previous studies indicate there are large differences in gastric cancer risk between men and women. This difference may be explained by the presence of estrogen receptors in gastric tissue and cancers (65). Decreased sex hormone levels or the cumulative effect of other conventional risk factors for gastric cancer in postmenopausal women may explain the observed differences by menopausal status.…”

Section: Discussionmentioning

confidence: 99%

One-Carbon Metabolism Dietary Factors and Distal Gastric Cancer Risk in Chinese Women

Kweon

Shu

Xiang

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background Previous studies on the association between one-carbon dietary factors and gastric cancer risk have been inconsistent. Methods We investigated this association using data from a prospective study, the Shanghai Women’s Health Study (1997–2010), including 323 distal gastric cancer cases identified from 73,009 Chinese women. Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazard regression after adjusting for confounders. Results Overall, no statistically significant association of gastric cancer was observed with dietary intake of folate, methionine, or B vitamins. However, when stratified by menopausal status, higher intake of riboflavin was associated with decreased gastric cancer risk in premenopausal women with HR of 0.35 (95% CI: 0.17, 0.73), 0.48 (0.24, 0.97), 0.28 ( 0.12, 0.65), and 0.23 (0.07, 0.91), respectively, for the quintile 2 to 5 intake groups compared to the lowest quintile intake (p for trend=0.02]. Among premenopausal women, highest intake of folate was associated with increased gastric cancer risk (HR: 2.62; 95% CI: 1.04, 6.59). There were no statistically significant associations observed among postmenopausal women. Conclusions These results suggest dietary factors involved in one-carbon metabolism are associated with gastric cancer risk among premenopausal women. Impact Riboflavin may be a protective factor and folate may be a risk factor for premenopausal gastric cancer.

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Expression of estrogen receptors in gastric cancer and their clinical significance

Abstract: Our results suggest that the presence of ER-β in gastric cancer could have a protective effect against invasiveness of gastric cancer. Further studies are needed to clarify the role of ER-β in gastric cancers.

Cited by 72 publications

References 28 publications

Overexpression of ERα inhibits proliferation and invasion of MKN28 gastric cancer cells by suppressing β-catenin

Overexpression of ERα inhibits proliferation and invasion of MKN28 gastric cancer cells by suppressing β-catenin

Clinicopathological characteristics and prognosis of signet ring cell carcinoma of the stomach

One-Carbon Metabolism Dietary Factors and Distal Gastric Cancer Risk in Chinese Women

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