Browse > Article
http://dx.doi.org/10.1007/s43188-021-00100-6

Estrogen exposure causes the progressive growth of SK-Hep1-derived tumor in ovariectomized mice  

Oh, Sungryong (College of Pharmacy, Duksung Women's University)
Kwon, Hee Jung (College of Pharmacy, Duksung Women's University)
Jung, Joohee (College of Pharmacy, Duksung Women's University)
Publication Information
Toxicological Research / v.38, no.1, 2022 , pp. 1-7 More about this Journal
Abstract
Liver cancer, one of the leading death causes, has diferent incidence and mortality rates in men and women. The infuencing factor is considered to estrogen. However, the role of estrogen in liver cancer remains controversial. In this study, we investigated the efects of estrogen on tumor progression. Total RNA sequencing was analyzed in SK-Hep1-derived tumor tissues, and 15 genes were expressed only in female mice. Among the diferentially expressed genes, matrix metalloprotease 7 (MMP7), germ cell associated 1 (GSG1), and chromosome 6 open reading frame 15 (C6orf15) were associated with signifcantly diferent overall survival rates based on their expression level in liver cancer patients. Interestingly, exogenous estrogen aggravated SK-Hep1-derived tumor growth in ovariectomized (OVX) mice. When OVX mice were treated with exogenous estrogen, SK-Hep1-derived tumor tissues exhibited high MMP7 expression levels and low GSG1 and C6orf15 expression levels. These expression patterns were consistent with those of liver cancer patients with low overall survival rates. These results suggest that these genes are expected to be prognostic biomarkers of liver cancer. In conclusion, our results suggest that continuous estrogen exposure may promote tumor growth in OVX mice.
Keywords
Ovariectomized mice; SK-Hep1 cells; Estrogen; Tumor growth;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Eun JR, Jung YJ, Zhang Y, Zhang Y, Tschudy-Seney B, Ramsamooj R, Wan YJ, Theise ND, Zern MA, Duan Y (2014) Hepatoma SK Hep-1 cells exhibit characteristics of oncogenic mesenchymal stem cells with highly metastatic capacity. PLoS ONE 9:e110744. https://doi.org/10.1371/journal.pone.0110744   DOI
2 Liao CH, Chang WS, Tsai CW, Hu PS, Wu HC, Hsu SW, Chen GL, Yueh TC, Shen TC, Hsia TC, Bau DT (2018) Association of matrix metalloproteinase-7 genotypes with the risk of bladder cancer. In Vivo 32:1045-1050. https://doi.org/10.21873/invivo.11345   DOI
3 Resende C, Thiel A, Machado JC, Ristimaki A (2011) Gastric cancer: basic aspects. Helicobacter 16(Suppl 1):38-44. https://doi.org/10.1111/j.1523-5378.2011.00879.x   DOI
4 Lin Y, Liu J, Huang Y, Liu D, Zhang G, Kan H (2017) micro-RNA-489 plays an anti-metastatic role in human hepatocellular carcinoma by targeting matrix metalloproteinase-7. Transl Oncol 10:211-220. https://doi.org/10.1016/j.tranon.2017.01.010   DOI
5 Park KU, Randazzo G, Jones KL, Brzezinski JAT (2017) Gsg1, Trnp1, and Tmem215 mark subpopulations of bipolar interneurons in the mouse retina. Investig Ophthalmol Vis Sci 58:1137-1150. https://doi.org/10.1167/iovs.16-19767   DOI
6 Mishra NK, Guda C (2017) Genome-wide DNA methylation analysis reveals molecular subtypes of pancreatic cancer. Oncotarget 8:28990-29012. https://doi.org/10.18632/oncotarget.15993   DOI
7 McGlynn KA, Sahasrabuddhe VV, Campbell PT, Graubard BI, Chen J, Schwartz LM, Petrick JL, Alavanja MC, Andreotti G, Boggs DA, Buring JE, Chan AT, Freedman ND, Gapstur SM, Hollenbeck AR, Hou L, King LY, Koshiol J, Linet M, Palmer JR, Poynter JN, Purdue M, Robien K, Schairer C, Sesso HD, Sigurdson A, Wactawski-Wende J, Zeleniuch-Jacquotte A (2015) Reproductive factors, exogenous hormone use and risk of hepatocellular carcinoma among US women: results from the Liver Cancer Pooling Project. Br J Cancer 112:1266-1272. https://doi.org/10.1038/bjc.2015.58   DOI
8 Wang R, Liu Y, Sun H, Wang T, Li C, Fan J, Wang Z (2021) Estradiol is signifcantly associated with prognosis in non-surgical liver cancer patients: from bench to bedside. Aging 13:3483-3500. https://doi.org/10.18632/aging.202280   DOI
9 Menyhart O, Nagy A, Gyorfy B (2018) Determining consistent prognostic biomarkers of overall survival and vascular invasion in hepatocellular carcinoma. R Soc Open Sci 5:181006. https://doi.org/10.1098/rsos.181006   DOI
10 Hefelfnger SC, Hawkins HH, Barrish J, Taylor L, Darlington GJ (1992) SK HEP-1: a human cell line of endothelial origin. Vitro Cell Dev Biol 28A:136-142. https://doi.org/10.1007/BF02631017   DOI
11 Iyer JK, Kalra M, Kaul A, Payton ME, Kaul R (2017) Estrogen receptor expression in chronic hepatitis C and hepatocellular carcinoma pathogenesis. World J Gastroenterol 23:6802-6816. https://doi.org/10.3748/wjg.v23.i37.6802   DOI
12 McGlynn KA, Hagberg K, Chen J, Braunlin M, Graubard BI, Suneja N, Jick S, Sahasrabuddhe VV (2016) Menopausal hormone therapy use and risk of primary liver cancer in the clinical practice research datalink. Int J Cancer 138:2146-2153. https://doi.org/10.1002/ijc.29960   DOI
13 Li Y, Xu A, Jia S, Huang J (2019) Recent advances in the molecular mechanism of sex disparity in hepatocellular carcinoma. Oncol Lett 17:4222-4228. https://doi.org/10.3892/ol.2019.10127   DOI
14 Jung KW, Won YJ, Hong S, Kong HJ, Lee ES (2020) Prediction of cancer incidence and mortality in Korea, 2020. Cancer Res Treat 52:351-358. https://doi.org/10.4143/crt.2020.203   DOI
15 Stratford JK, Bentrem DJ, Anderson JM, Fan C, Volmar KA, Marron JS, Routh ED, Caskey LS, Samuel JC, Der CJ, Thorne LB, Calvo BF, Kim HJ, Talamonti MS, Iacobuzio-Donahue CA, Hollingsworth MA, Perou CM, Yeh JJ (2010) A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma. PLoS Med 7:e1000307. https://doi.org/10.1371/journal.pmed.1000307   DOI
16 Le Large TYS, Bijlsma MF, Kazemier G, van Laarhoven HWM, Giovannetti E, Jimenez CR (2017) Key biological processes driving metastatic spread of pancreatic cancer as identifed by multiomics studies. Semin Cancer Biol 44:153-169. https://doi.org/10. 1016/j.semcancer.2017.03.008   DOI
17 Wall EH, Hewitt SC, Case LK, Lin CY, Korach KS, Teuscher C (2014) The role of genetics in estrogen responses: a critical piece of an intricate puzzle. FASEB J 28:5042-5054. https://doi.org/10.1096/f.14-260307   DOI
18 Taneja V (2018) Sex hormones determine immune response. Front Immunol 9:1931. https://doi.org/10.3389/fmmu.2018.01931   DOI
19 El-Serag HB, Sweet S, Winchester CC, Dent J (2014) Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut 63:871-880. https://doi.org/10.1136/gutjnl-2012-304269   DOI
20 Wei Q, Guo P, Mu K, Zhang Y, Zhao W, Huai W, Qiu Y, Li T, Ma X, Liu Y, Chen X, Han L (2015) Estrogen suppresses hepatocellular carcinoma cells through ERbeta-mediated upregulation of the NLRP3 infammasome. Lab Investig 95:804-816. https://doi.org/10.1038/labinvest.2015.63   DOI
21 Shimizu I, Kohno N, Tamaki K, Shono M, Huang HW, He JH, Yao DF (2007) Female hepatology: favorable role of estrogen in chronic liver disease with hepatitis B virus infection. World J Gastroenterol 13:4295-4305. https://doi.org/10.3748/wjg.v13.i32.4295   DOI
22 Yager JD Jr, Yager R (1980) Oral contraceptive steroids as promoters of hepatocarcinogenesis in female Sprague-Dawley rats. Can Res 40:3680-3685
23 Lee S, Kim KM, Lee SY, Jung J (2021) Estrogen aggravates tumor growth in a difuse gastric cancer xenograft model. Pathol Oncol Res 27:1-9. https://doi.org/10.3389/pore.2021.622733   DOI
24 Scheau C, Badarau IA, Costache R, Caruntu C, Mihai GL, Didilescu AC, Constantin C, Neagu M (2019) The role of matrix metalloproteinases in the epithelial-mesenchymal transition of hepatocellular carcinoma. Anal Cell Pathol 2019:9423907. https://doi.org/10.1155/2019/9423907   DOI
25 Ohta R, Takagi A, Ohmukai H, Marumo H, Ono A, Matsushima Y, Inoue T, Ono H, Kanno J (2012) Ovariectomized mouse uterotrophic assay of 36 chemicals. J Toxicol Sci 37:879-889. https://doi.org/10.2131/jts.37.879   DOI
26 Yu B, Liu X, Chang H (2017) MicroRNA-143 inhibits colorectal cancer cell proliferation by targeting MMP7. Minerva Med 108:13-19. https://doi.org/10.23736/S0026-4806.16.04651-6   DOI
27 Endeshaw M, Hallowell BD, Razzaghi H, Senkomago V, McKenna MT, Saraiya M (2019) Trends in liver cancer mortality in the United States: dual burden among foreign- and US-born persons. Cancer 125:726-734. https://doi.org/10.1002/cncr.31869   DOI
28 Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394-424. https://doi.org/10.3322/caac.21492   DOI
29 Chaturantabut S, Shwartz A, Evason KJ, Cox AG, Labella K, Schepers AG, Yang S, Acuna M, Houvras Y, Mancio-Silva L, Romano S, Gorelick DA, Cohen DE, Zon LI, Bhatia SN, North TE, Goessling W (2019) Estrogen activation of G-protein-coupled estrogen receptor 1 regulates phosphoinositide 3-kinase and mTOR signaling to promote liver growth in zebrafsh and proliferation of human hepatocytes. Gastroenterology 156:1788-1804. e1713. https://doi.org/10.1053/j.gastro.2019.01.010   DOI
30 Wanless IR, Medline A (1982) Role of estrogens as promoters of hepatic neoplasia. Lab Investig 46:313-320
31 Oh S, Choi K, Kim KM, Jung J (2020) Sex-dependent efects of estrogen pellets in human liver cancer xenograft models. Toxicol Res 36:109-114. https://doi.org/10.1007/s43188-019-00020-6   DOI
32 Brohawn DG, O'Brien LC, Bennett JP Jr (2016) RNAseq analyses identify tumor necrosis factor-mediated infammation as a major abnormality in ALS spinal cord. PLoS ONE 11:e0160520. https://doi.org/10.1371/journal.pone.0160520   DOI
33 Shi L, Feng Y, Lin H, Ma R, Cai X (2014) Role of estrogen in hepatocellular carcinoma: is infammation the key? J Transl Med 12:93. https://doi.org/10.1186/1479-5876-12-93   DOI
34 Villa E (2008) Role of estrogen in liver cancer. Womens Health 4:41-50. https://doi.org/10.2217/17455057.4.1.41   DOI
35 Montella M, D'Arena G, Crispo A, Capunzo M, Nocerino F, Grimaldi M, Barbieri A, D'Ursi AM, Tecce MF, Amore A, Galdiero M, Ciliberto G, Giudice A (2015) Role of sex hormones in the development and progression of hepatitis B virus-associated hepatocellular carcinoma. Int J Endocrinol 2015:854530. https://doi.org/10.1155/2015/854530   DOI
36 Sarver AE, Sarver AL, Thayanithy V, Subramanian S (2015) Identifcation, by systematic RNA sequencing, of novel candidate biomarkers and therapeutic targets in human soft tissue tumors. Lab Investig 95:1077-1088. https://doi.org/10.1038/labinvest.2015.80   DOI
37 Zheng W, Zou Z, Lin S, Chen X, Wang F, Li X, Dai J (2019) Identifcation and functional analysis of spermatogenesis-associated gene modules in azoospermia by weighted gene coexpression network analysis. J Cell Biochem 120:3934-3944. https://doi.org/10.1002/jcb.27677   DOI