Imbalanced Expression Pattern of Steroid Receptor Coactivator-1 and -3 in Liver Cancer Compared with Normal Liver: An Immunohistochemical Study with Tissue Microarray

Overview

Journal Oncol Lett

Specialty Oncology

Date 2018 Nov 9

PMID 30405769

Citations 1

Authors

Shan Li

Huiyan Zhang

Yanlan Yu

Mengying Liu

Deyu Guo

Xuqing Zhang

Jiqiang Zhang

Affiliations

Soon will be listed here.

Abstract

Steroids affect normal and pathological functions of the liver through receptors, which require coactivators for their transcriptional activation. Steroid receptor coactivator (SRC)-1 and SRC-3 have been demonstrated to be regulated in numerous cancers; however, their expression profiles in liver cancer including hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC) remain unclear. Using tissue microarray immunohistochemistry, normal liver tissue and HCC tissue exhibited immunoreactivity of SRC-1, which were predominantly localized within extranuclear components; in CCC, they were detected within the cell nuclei; SRC-3 was also detected in the cell nuclei. Furthermore, no altered expression of SRC-1 and SRC-3 was observed in liver cancer compared with normal liver tissue; however, in CCC, the expression of SRC-3 was significantly increased compared with that detected in HCC. Importantly, although expression of SRC-1 and SRC-3 did not reveal any significant differences (30 vs. 40%) in normal liver tissue, HCC and CCC expression of SRC-1 was significantly decreased compared with that of SRC-3 (9.3 vs. 36%, and 6.7 vs. 67.7% for HCC and CCC, respectively). Further comparative analysis revealed that this discrepancy was detected in males with liver cancer, across all ages of HCC cases, younger CCC cases and all stages of liver cancer. The results suggested the presence of an imbalanced expression pattern of SRC-1 and SRC-3 from normal liver tissue to liver cancer (decreased SRC-1 and increased SRC-3), which may affect hepatic function and therefore promote liver carcinogenesis.

Citing Articles

Different Coactivator Recruitment to Human PPARα/δ/γ Ligand-Binding Domains by Eight PPAR Agonists to Treat Nonalcoholic Fatty Liver Disease.

Kamata S, Honda A, Kashiwagi N, Shimamura A, Yashiro S, Komori Y Biomedicines. 2024; 12(3).

PMID: 38540237 PMC: 10967972. DOI: 10.3390/biomedicines12030624.

References

Van Sinderen M, Steinberg G, Jorgensen S, To S, Knower K, Clyne C . Hepatic glucose intolerance precedes hepatic steatosis in the male aromatase knockout (ArKO) mouse. PLoS One. 2014; 9(2):e87230. PMC: 3919708. DOI: 10.1371/journal.pone.0087230. View

Uchikawa J, Shiozawa T, Shih H, Miyamoto T, Feng Y, Kashima H . Expression of steroid receptor coactivators and corepressors in human endometrial hyperplasia and carcinoma with relevance to steroid receptors and Ki-67 expression. Cancer. 2003; 98(10):2207-13. DOI: 10.1002/cncr.11760. View

York B, OMalley B . Steroid receptor coactivator (SRC) family: masters of systems biology. J Biol Chem. 2010; 285(50):38743-50. PMC: 2998129. DOI: 10.1074/jbc.R110.193367. View

Wang B, Chen L, Chang H . Potential diagnostic and prognostic biomarkers for cholangiocarcinoma in serum and bile. Biomark Med. 2016; 10(6):613-9. DOI: 10.2217/bmm-2015-0062. View

Wang H, Zhang D, Wu W, Zhang J, Guo D, Wang Q . Overexpression and gender-specific differences of SRC-3 (SRC-3/AIB1) immunoreactivity in human non-small cell lung cancer: an in vivo study. J Histochem Cytochem. 2010; 58(12):1121-7. PMC: 2989248. DOI: 10.1369/jhc.2010.956979. View

Xu J, Wu R, OMalley B . Normal and cancer-related functions of the p160 steroid receptor co-activator (SRC) family. Nat Rev Cancer. 2009; 9(9):615-30. PMC: 2908510. DOI: 10.1038/nrc2695. View

Yang D, Hanna D, Usher J, LoCoco J, Chaudhari P, Lenz H . Impact of sex on the survival of patients with hepatocellular carcinoma: a Surveillance, Epidemiology, and End Results analysis. Cancer. 2014; 120(23):3707-16. PMC: 9191612. DOI: 10.1002/cncr.28912. View

Sheng M, Xu G, Zhang C, Jia W, Ren W, Liu W . Aberrant estrogen receptor alpha expression correlates with hepatocellular carcinoma metastasis and its mechanisms. Hepatogastroenterology. 2014; 61(129):146-50. View

Sinclair M, Gow P, Angus P, Hoermann R, Handelsman D, Wittert G . High circulating oestrone and low testosterone correlate with adverse clinical outcomes in men with advanced liver disease. Liver Int. 2016; 36(11):1619-1627. DOI: 10.1111/liv.13122. View

10.

Xu F, Xie D, Wen J, Wu H, Liu Y, Bi J . SRC-3/AIB1 protein and gene amplification levels in human esophageal squamous cell carcinomas. Cancer Lett. 2006; 245(1-2):69-74. DOI: 10.1016/j.canlet.2005.12.030. View

11.

Hunsawong T, Singsuksawat E, In-chon N, Chawengrattanachot W, Thuwajit C, Sripa B . Estrogen is increased in male cholangiocarcinoma patients' serum and stimulates invasion in cholangiocarcinoma cell lines in vitro. J Cancer Res Clin Oncol. 2012; 138(8):1311-20. DOI: 10.1007/s00432-012-1207-1. View

12.

Hata S, Miki Y, Saito R, Ishida K, Watanabe M, Sasano H . Aromatase in human liver and its diseases. Cancer Med. 2013; 2(3):305-15. PMC: 3699842. DOI: 10.1002/cam4.85. View

13.

Brady C . Liver disease in menopause. World J Gastroenterol. 2015; 21(25):7613-20. PMC: 4491951. DOI: 10.3748/wjg.v21.i25.7613. View

14.

Louet J, Chopra A, Sagen J, An J, York B, Tannour-Louet M . The coactivator SRC-1 is an essential coordinator of hepatic glucose production. Cell Metab. 2010; 12(6):606-18. PMC: 3024581. DOI: 10.1016/j.cmet.2010.11.009. View

15.

Yoshida H, Liu J, Samuel S, Cheng W, Rosen D, Naora H . Steroid receptor coactivator-3, a homolog of Taiman that controls cell migration in the Drosophila ovary, regulates migration of human ovarian cancer cells. Mol Cell Endocrinol. 2005; 245(1-2):77-85. DOI: 10.1016/j.mce.2005.10.008. View

16.

Singsuksawat E, Thuwajit C, Charngkaew K, Thuwajit P . Increased ETV4 expression correlates with estrogen-enhanced proliferation and invasiveness of cholangiocarcinoma cells. Cancer Cell Int. 2018; 18:25. PMC: 5819217. DOI: 10.1186/s12935-018-0525-z. View

17.

Isse K, Specht S, Lunz 3rd J, Kang L, Mizuguchi Y, Demetris A . Estrogen stimulates female biliary epithelial cell interleukin-6 expression in mice and humans. Hepatology. 2010; 51(3):869-80. DOI: 10.1002/hep.23386. View

18.

Li W, Fu J, Bian C, Zhang J, Xie Z . Immunohistochemical localization of steroid receptor coactivators in chondrosarcoma: an in vivo tissue microarray study. Pathol Res Pract. 2014; 210(12):1005-10. DOI: 10.1016/j.prp.2014.04.012. View

19.

Qin L, Chen X, Wu Y, Feng Z, He T, Wang L . Steroid receptor coactivator-1 upregulates integrin α₅ expression to promote breast cancer cell adhesion and migration. Cancer Res. 2011; 71(5):1742-51. PMC: 3076137. DOI: 10.1158/0008-5472.CAN-10-3453. View

20.

Xie D, Sham J, Zeng W, Lin H, Bi J, Che L . Correlation of AIB1 overexpression with advanced clinical stage of human colorectal carcinoma. Hum Pathol. 2005; 36(7):777-83. DOI: 10.1016/j.humpath.2005.05.007. View