Expression analysis of the estrogen receptor target genes in renal cell carcinoma

Liu,Zhihong; Lu,You; He,Zonghai; Chen,Libo; Lu,Yiping

doi:10.3892/mmr.2014.2766

Expression analysis of the estrogen receptor target genes in renal cell carcinoma

Authors:
- Zhihong Liu
- You Lu
- Zonghai He
- Libo Chen
- Yiping Lu
View Affiliations

Affiliations: Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
Published online on: October 24, 2014 https://doi.org/10.3892/mmr.2014.2766
Pages: 75-82
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to investigate the differentially expressed genes (DEGs) and target genes of the estrogen receptor (ER) in renal cell carcinoma. The data (GSE12090) were downloaded from the gene expression omnibus database. Data underwent preprocessing using the affy package for Bioconductor software, then the DEGs were selected via the significance analysis of microarray algorithm within the siggenes package. Subsequently, the DEGs underwent functional and pathway enrichment analysis using Database for Annotation Visualization and Integrated Discovery software. Following data analysis, transcriptional regulatory networks between the DEGs and transcription factors were constructed. Finally, the ER target genes were subjected to gene ontology enrichment analysis. A total of 215 DEGs were identified between the chromophobe renal cell carcinoma samples and the oncocytoma samples, including 126 upregulated and 89 downregulated genes. Functional enrichment analysis indicated that 25% of the DEGs were significantly enriched in functions associated with the plasma membrane. Among those DEGs, 105 were regulated by the ER. Further regulatory network analysis indicated that the ER was mainly involved in the regulation of oncogenes and tumor suppressor genes, including protease serine 8, claudin 7 and Ras‑related protein Rab‑25. In the present study, the identified ER target genes were demonstrated to be closely associated with tumor development; this knowledge may improve the understanding of the ER regulatory mechanisms during tumor development and promote the discovery of predictive markers for renal cell carcinoma.

View Figures

View References

1	Gottardo F, Liu CG, Ferracin M, et al: Micro-RNA profiling in kidney and bladder cancers. Urol Oncol. 25:387–392. 2007. View Article : Google Scholar : PubMed/NCBI
2	Chow TF, Youssef YM, Lianidou E, et al: Differential expression profiling of microRNAs and their potential involvement in renal cell carcinoma pathogenesis. Clin Biochem. 43:150–158. 2010. View Article : Google Scholar : PubMed/NCBI
3	Yi ZJ, Fu YR, Zhao SS, et al: Differential expression of miRNA patterns in renal cell carcinoma and nontumorous tissues. J Cancer Res Clin Oncol. 136:855–862. 2010. View Article : Google Scholar : PubMed/NCBI
4	Ljungberg B, Cowan NC, Hanbury DC, et al: EAU guidelines on renal cell carcinoma: the 2010 update. Euro Urology. 58:398–406. 2010. View Article : Google Scholar : PubMed/NCBI
5	Janzen NK, Kim HL, Figlin RA, et al: Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease. Urologic Clinics of North America. 30:843–852. 2003. View Article : Google Scholar : PubMed/NCBI
6	Kondo K, Yao M, Yoshida M, et al: Comprehensive mutational analysis of the VHL gene in sporadic renal cell carcinoma: relationship to clinicopathological parameters. Genes, Chromosomes and Cancer. 34:58–68. 2002. View Article : Google Scholar : PubMed/NCBI
7	Maxwell PH, Wiesener MS, Chang GW, et al: The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature. 399:271–275. 1999. View Article : Google Scholar : PubMed/NCBI
8	Rini BI, Campbell SC and Escudier B: Renal cell carcinoma. Lancet. 373:1119–1132. 2009. View Article : Google Scholar : PubMed/NCBI
9	Dalgliesh GL, Furge K, Greenman C, et al: Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature. 463:360–363. 2010. View Article : Google Scholar
10	Varela I, Tarpey P, Raine K, et al: Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature. 469:539–542. 2011. View Article : Google Scholar : PubMed/NCBI
11	Fiorito E, Katika MR and Hurtado A: Cooperating transcription factors mediate the function of estrogen receptor. Chromosoma. 122:1–12. 2013. View Article : Google Scholar : PubMed/NCBI
12	Musgrove EA and Sutherland RL: Biological determinants of endocrine resistance in breast cancer. Nat Rev Cancer. 9:631–643. 2009. View Article : Google Scholar : PubMed/NCBI
13	Harigopal M, Heymann J, Ghosh S, Anagnostou V, Camp RL and Rimm DL: Estrogen receptor co-activator (AIB1) protein expression by automated quantitative analysis (AQUA) in a breast cancer tissue microarray and association with patient outcome. Breast Cancer Res Treat. 115:77–85. 2009. View Article : Google Scholar
14	Ross-Innes CS, Stark R, Teschendorff AE, et al: Differential oestrogen receptor binding is associated with clinical outcome in breast cancer. Nature. 481:389–393. 2012.PubMed/NCBI
15	Ross-Innes CS, Stark R, Holmes KA, et al: Cooperative interaction between retinoic acid receptor-alpha and estrogen receptor in breast cancer. Genes Dev. 24:171–182. 2010. View Article : Google Scholar : PubMed/NCBI
16	Grober OM, Mutarelli M, Giurato G, et al: Global analysis of estrogen receptor beta binding to breast cancer cell genome reveals an extensive interplay with estrogen receptor alpha for target gene regulation. BMC Genomics. 12:362011. View Article : Google Scholar : PubMed/NCBI
17	Tan MH, Wong CF, Tan HL, et al: Genomic expression and single-nucleotide polymorphism profiling discriminates chromophobe renal cell carcinoma and oncocytoma. BMC Cancer. 10:1962010. View Article : Google Scholar : PubMed/NCBI
18	Gentleman RC, Carey VJ, Bates DM, et al: Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 5:R802004. View Article : Google Scholar : PubMed/NCBI
19	Schwender H, Krause A and Ickstadt K: Identifying interesting genes with siggenes [J]. The Newsletter of the R Project. 6:45–50. 2006.
20	Dennis G Jr, Sherman BT, Hosack DA, et al: DAVID: Database for annotation, visualization, and integrated discovery. Genome Biol. 4:P32003. View Article : Google Scholar : PubMed/NCBI
21	Fujita PA, Rhead B, Zweig AS, et al: The UCSC genome browser database: update 2011. Nucleic Acids Res. 39:D876–D882. 2011. View Article : Google Scholar : PubMed/NCBI
22	Shannon P, Markiel A, Ozier O, et al: Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13:2498–2504. 2003. View Article : Google Scholar : PubMed/NCBI
23	Zheng Q and Wang XJ: GOEAST: a web-based software toolkit for Gene Ontology enrichment analysis. Nucleic Acids Res. 36:W358–W363. 2008. View Article : Google Scholar : PubMed/NCBI
24	Chen M, Chen LM, Lin CY and Chai KX: The epidermal growth factor receptor (EGFR) is proteolytically modified by the Matriptase-Prostasin serine protease cascade in cultured epithelial cells. BBA-Mol Cell Res. 1783:896–903. 2008.
25	Chen M, Fu YY, Lin CY, Chen LM and Chai KX: Prostasin induces protease-dependent and independent molecular changes in the human prostate carcinoma cell line PC-3. Bioch Biophys Acta. 1773:1133–1140. 2007. View Article : Google Scholar : PubMed/NCBI
26	Chen LM, Verity NJ and Chai KX: Loss of prostasin (PRSS8) in human bladder transitional cell carcinoma cell lines is associated with epithelial-mesenchymal transition (EMT). BMC Cancer. 9:3772009. View Article : Google Scholar : PubMed/NCBI
27	Sakashita K, Mimori K, Tanaka F, et al: Clinical significance of low expression of Prostasin mRNA in human gastric cancer. J Surg Oncol. 98:559–564. 2008. View Article : Google Scholar : PubMed/NCBI
28	Chen LM, Zhang X and Chai KX: Regulation of prostasin expression and function in the prostate. Prostate. 59:1–12. 2004. View Article : Google Scholar : PubMed/NCBI
29	Zhu Y, Brännström M, Janson PO, et al: Differences in expression patterns of the tight junction proteins, claudin 1, 3, 4 and 5, in human ovarian surface epithelium as compared to epithelia in inclusion cysts and epithelial ovarian tumours. Int J cancer. 118:1884–1891. 2006. View Article : Google Scholar
30	Usami Y, Chiba H, Nakayama F, et al: Reduced expression of claudin-7 correlates with invasion and metastasis in squamous cell carcinoma of the esophagus. Hum Pathol. 37:569–577. 2006. View Article : Google Scholar : PubMed/NCBI
31	Tassi RA, Bignotti E, Falchetti M, et al: Claudin-7 expression in human epithelial ovarian cancer. Int J Gynecol Cancer. 18:1262–1271. 2008. View Article : Google Scholar : PubMed/NCBI
32	Lioni M, Brafford P, Andl C, et al: Dysregulation of claudin-7 leads to loss of E-cadherin expression and the increased invasion of esophageal squamous cell carcinoma cells. Am J Pathol. 170:709–721. 2007. View Article : Google Scholar : PubMed/NCBI
33	Cheng KW, Lahad JP, Kuo WL, et al: The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers. Nat Med. 10:1251–1256. 2004. View Article : Google Scholar : PubMed/NCBI
34	Calhoun BC and Goldenring J: Rab proteins in gastric parietal cells: evidence for the membrane recycling hypothesis. Yale J Biol Med. 69:1–8. 1996.PubMed/NCBI
35	Cheng JM, Volk L, Janaki DK, Vyakaranam S, Ran S and Rao KA: Tumor suppressor function of Rab25 in triple-negative breast cancer. Int J Cancer. 126:2799–2812. 2010.PubMed/NCBI
36	Cheng KW, Agarwal R, Mitra S, et al: Rab25 increases cellular ATP and glycogen stores protecting cancer cells from bioenergetic stress. EMBO Mol Med. 4:125–141. 2012. View Article : Google Scholar : PubMed/NCBI
37	Dozynkiewicz MA, Jamieson NB, MacPherson I, et al: Rab25 and CLIC3 collaborate to promote integrin recycling from late endosomes/lysosomes and drive cancer progression. Dev Cell. 22(1): 131–145. 2012. View Article : Google Scholar : PubMed/NCBI
38	Amornphimoltham P, Rechache K, Thompson J, et al: Rab25 regulates invasion and metastasis in head and neck cancer. Clin Cancer Res. 19:1375–1388. 2013. View Article : Google Scholar : PubMed/NCBI
39	Lappano R and Maggiolini M: G protein-coupled receptors: novel targets for drug discovery in cancer. Nat Rev Drug Discov. 10:47–60. 2011. View Article : Google Scholar : PubMed/NCBI
40	Mócsai A, Ruland J and Tybulewicz VL: The SYK tyrosine kinase: a crucial player in diverse biological functions. Nat Rev Immunol. 10:387–402. 2010.PubMed/NCBI
41	Sun T, Aceto N, Meerbrey KL, et al: Activation of multiple proto-oncogenic tyrosine kinases in breast cancer via loss of the PTPN12 phosphatase. Cell. 144:703–718. 2011. View Article : Google Scholar : PubMed/NCBI