The direct effect of estrogen on cell viability and apoptosis in human gastric cancer cells
- 473 Downloads
Epidemiology researches indicated that gastric cancer is a male-predominant disease; both expression level of estrogen and expression pattern of estrogen receptors (ERs) influence its carcinogenesis. But the direct effect of estrogen on gastric cancer cells is still unclear. This study aimed to explore the direct effect of β-estradiol (E2) on gastric cancer cells. SGC7901 and BGC823 were treated with a serial of concentrations of E2. The survival rates of both the cell lines were significantly reduced, and the reduction of viability was due to apoptosis triggered by E2 treatment. Caspase 3 was activated in response to the increasing E2 concentration in both SGC7901 and BGC823. Cleaved Caspase 3 fragments were detected, and the expression levels of Bcl-2 and Bcl-xL were reduced. Apoptosis was further confirmed by flow cytometry. The expression level of PEG10, an androgen receptor target gene, was reduced during E2 treatment. Both ERα and ERβ were expressed in these cell lines, and the result of bioinformatics analysis of gastric cancer from GEO datasets indicated that the expression levels of both ERα and ERβ were significantly higher in noncancerous gastric tissues than in gastric cancer tissues. Our research indicated that estrogen can reduce cell viability and promote apoptosis in gastric cancer cells directly; ERs expression level is associated with gastric cancer. Our research will help to understand the mechanism of gender disparity in gastric cancer.
KeywordsGender disparity Estrogen Estrogen receptor Apoptosis PEG10
Q. J. and L. M. contributed equally to this work. The study was supported by the Hubei Province Natural Science Foundation of China (No. 2012FFB04316), the National Natural Science Foundation of China (No. 30801336 and No. 81102863), and The Incubator Project of Renmin Hospital Wuhan University (2013RMFH008). All authors of the manuscript have contributed to this work.
- 6.Ohtani M, Garcia A, Rogers AB, Ge Z, Taylor NS, Xu S, Watanabe K, Marini RP, Whary MT, Wang TC, Fox JG (2007) Protective role of 17 beta -estradiol against the development of Helicobacter pylori-induced gastric cancer in INS-GAS mice. Carcinogenesis 28(12):2597–2604. doi: 10.1093/carcin/bgm150 PubMedCrossRefGoogle Scholar
- 7.Ohtani M, Ge Z, Garcia A, Rogers AB, Muthupalani S, Taylor NS, Xu S, Watanabe K, Feng Y, Marini RP, Whary MT, Wang TC, Fox JG (2011) 17 beta-estradiol suppresses Helicobacter pylori-induced gastric pathology in male hypergastrinemic INS-GAS mice. Carcinogenesis 32(8):1244–1250. doi: 10.1093/carcin/bgr072 PubMedCentralPubMedCrossRefGoogle Scholar
- 10.Ma WL, Hsu CL, Wu MH, Wu CT, Wu CC, Lai JJ, Jou YS, Chen CW, Yeh S, Chang C (2008) Androgen receptor is a new potential therapeutic target for the treatment of hepatocellular carcinoma. Gastroenterology 135(3):947–955. doi: 10.1053/j.gastro.2008.05.046 955 e941–945PubMedCentralPubMedCrossRefGoogle Scholar
- 13.Wang M, Pan JY, Song GR, Chen HB, An LJ, Qu SX (2007) Altered expression of estrogen receptor alpha and beta in advanced gastric adenocarcinoma: correlation with prothymosin alpha and clinicopathological parameters. Eur J Surg Oncol 33(2):195–201. doi: 10.1016/j.ejso.2006.09.009 PubMedCrossRefGoogle Scholar
- 15.Feng H, Cheng AS, Tsang DP, Li MS, Go MY, Cheung YS, Zhao GJ, Ng SS, Lin MC, Yu J, Lai PB, To KF, Sung JJ (2011) Cell cycle-related kinase is a direct androgen receptor-regulated gene that drives beta-catenin/T cell factor-dependent hepatocarcinogenesis. J Clin Investig 121(8):3159–3175. doi: 10.1172/JCI45967 PubMedCentralPubMedCrossRefGoogle Scholar
- 16.Okabe H, Satoh S, Kato T, Kitahara O, Yanagawa R, Yamaoka Y, Tsunoda T, Furukawa Y, Nakamura Y (2001) Genome-wide analysis of gene expression in human hepatocellular carcinomas using cDNA microarray: identification of genes involved in viral carcinogenesis and tumor progression. Cancer Res 61(5):2129–2137PubMedGoogle Scholar
- 19.Chunsong H, Yuling H, Li W, Jie X, Gang Z, Qiuping Z, Qingping G, Kejian Z, Li Q, Chang AE, Youxin J, Jinquan T (2006) CXC chemokine ligand 13 and CC chemokine ligand 19 cooperatively render resistance to apoptosis in B cell lineage acute and chronic lymphocytic leukemia CD23+ CD5+ B cells. J Immunol 177(10):6713–6722PubMedCrossRefGoogle Scholar
- 26.Dai Y, Chen S, Wang L, Pei XY, Funk VL, Kramer LB, Dent P, Grant S (2011) Disruption of IkappaB kinase (IKK)-mediated RelA serine 536 phosphorylation sensitizes human multiple myeloma cells to histone deacetylase (HDAC) inhibitors. J Biol Chem 286(39):34036–34050PubMedCentralPubMedCrossRefGoogle Scholar
- 28.Chaudhri RA, Olivares-Navarrete R, Cuenca N, Hadadi A, Boyan BD, Schwartz Z (2012) Membrane estrogen signaling enhances tumorigenesis and metastatic potential of breast cancer cells via estrogen receptor-alpha36 (ERalpha36). J Biol Chem 287(10):7169–7181. doi: 10.1074/jbc.M111.292946 PubMedCentralPubMedCrossRefGoogle Scholar