Endogenous estrogen exposure in relation to distribution of histological type and estrogen receptors in gastric adenocarcinoma

Chandanos, Evangelos; Rubio, Carlos A.; Lindblad, Mats; Jia, Chongqi; Tsolakis, Apostolos V.; Warner, Margaret; Gustafsson, Jan Åke; Lagergren, Jesper

doi:10.1007/s10120-008-0475-6

Cited by 33 publications

(28 citation statements)

References 45 publications

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“…The other reasons may involve that higher estradiol (E2) levels in U.S. people were reported in each gender possible related to the higher BMI compared with those in Japan [41,42]. Moreover, expression rates of ER-α and -β in gastric cancer by IHC in Asian population were 0% to 22.7 % and 43.6 % to 100 %, respectively [43,44], whereas those in Western population were 36 % and 11 %, respectively [45]. These physiologic and biologic differences among gender and region may impact the protective estrogen effect in gastric cancer, and also affect the impact of the c-MET pathway on clinical outcome through the cross-talk such as the EGFR or Wnt pathway.…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of the c-MET polymorphism on the clinical outcome in locoregional gastric cancer patients

Sunakawa

Wakatsuki²,

Yang³

et al. 2014

Pharmacogenetics and Genomics

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Objective Dysregulation of c-MET signaling pathway results from various molecular mechanisms including mutations, amplification, and overexpression. Overexpression and amplification of c-MET have been correlated with poor clinical outcome in gastric cancer, whereas the associations between c-MET polymorphisms and prognosis have not been well defined. We examined the prognostic impact of functional polymorphisms of MET gene on clinical outcome in gastric cancer. Methods Candidate polymorphisms of MET gene were analyzed by PCR-based direct sequencing for the associations with clinical outcome across three independent cohorts, including 161 Japanese, 101 U.S. and 63 Austrian patients, with loco-regional gastric cancer treated with surgery. Results The univariable analysis showed patients with any G (A/G or G/G genotype) allele of MET rs40239 had significantly longer disease-free survival and overall survival compared to those with the AA genotype in the Japanese cohort (HR: 0.43; P=0.001, HR: 0.47; P=0.006, respectively); this remained significant upon multivariable analysis adjusted for age, sex, stage, and type of adjuvant therapy (HR: 0.48; P=0.009, HR: 0.50; P=0.017, respectively). However, there was no significant association of the polymorphism with clinical outcome in the U.S. and Austrian cohort. When stratified by gender in the Japanese cohort, males, but not females, with the G allele maintained a clinical outcome benefit in both univariable and multivariable analysis. Conclusions The MET rs40239 may serve as a prognostic biomarker in loco-regional gastric cancer. These data also suggest that genetic variants of the c-MET may have a gender-related difference in the impact on clinical outcome.

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Section: Discussionmentioning

confidence: 99%

Prognostic impact of the c-MET polymorphism on the clinical outcome in locoregional gastric cancer patients

Sunakawa

Wakatsuki²,

Yang³

et al. 2014

Pharmacogenetics and Genomics

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“…Oestrogen-bound ERs bind as homodimers or heterodimers to a specific DNA sequence known as the oestrogen-responsive element (ERE), and regulate the transcription of target genes (Matthews and Gustafsson, 2003). As oestrogen is a stimulant for the initiation and promotion of breast cancer, and ERa can be expressed in gastric cancer cells, it has been suggested that the ERa pathway may have a role in the progression of gastric cancer (Harrison et al, 1989b;Wu et al, 1994;Karat et al, 1999;Takano et al, 2002;Chandanos et al, 2008). In gastric cancer, ERa expression is higher in the diffuse type than in the intestinal type (Kitaoka, 1983;Tokunaga et al, 1986;Matsui et al, 1992;Zhao et al, 2003), and oestradiol (E2) enhances gastric cancer cell proliferation in vitro (Matsui et al, 1992;Takano et al, 2002).…”

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confidence: 99%

Oestrogen receptor-α contributes to the regulation of the hedgehog signalling pathway in ERα-positive gastric cancer

et al. 2010

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BACKGROUND: Oestrogen receptor-alpha (ERa) is highly expressed in diffuse-type gastric cancer and oestrogen increases the proliferation of ERa-positive gastric cancer. However, a detailed mechanism by which oestrogen increases the proliferation of these cells is still unclear. METHODS: We used 17-b-oestradiol (E2) as a stimulator against the ERa pathway. Pure anti-oestrogen drug ICI 182 780 (ICI) and small interfering RNA against ERa (ERa siRNA) were used as inhibitors. Cyclopamine (Cyc) was used as the hedgehog (Hh) pathway inhibitor. Two human ERa-positive gastric cancer cells were used as target cells. Effects of the stimulator and inhibitor on E2-induced cell proliferation were also examined. RESULTS: In ERa-positive cells, E2 increased not only cell proliferation but also one of the ligands of the Hh pathway, Shh expression. 17-b-Oestradiol-induced cell proliferation was suppressed by ICI, ERa siRNA or Cyc. The increased expression of Shh induced by E2 was suppressed by ICI and ERa siRNA but not by Cyc. Furthermore, recombinant Shh activated the Hh pathway and increased cell proliferation, whereas anti-Shh antibody suppressed E2-induced cell proliferation. When a relationship between ERa and Shh expressions was analysed using surgically resected gastric cancer specimens, a positive correlation was found, suggesting a linkage between the ERa and Hh pathways. CONCLUSION: Our data indicate that activation of the ERa pathway promotes cell proliferation by activating the Hh pathway in a ligand-dependent manner through Shh induction of ERa-positive gastric cancer.

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“…Recent studies have shown conflicting results of ERα expression in gastric cancer (13,14). Moreover, when using the immunohistochemical method, the expression of ERα gastric cancer tissues showed marked variability (0-62.5%) among a number of studies (15)(16)(17).…”

Section: Discussionmentioning

confidence: 99%

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

Wang¹,

Fang³

et al. 2011

Oncology Letters

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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.

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Endogenous estrogen exposure in relation to distribution of histological type and estrogen receptors in gastric adenocarcinoma

Cited by 33 publications

References 45 publications

Prognostic impact of the c-MET polymorphism on the clinical outcome in locoregional gastric cancer patients

Prognostic impact of the c-MET polymorphism on the clinical outcome in locoregional gastric cancer patients

Oestrogen receptor-α contributes to the regulation of the hedgehog signalling pathway in ERα-positive gastric cancer

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

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