Abstract
Our preliminary study indicated that Engrailed-2 (EN2) is downregulated but also ectopically expressed in clear-cell renal cell carcinoma (CCRCC), and the absence of EN2 expression was associated with poor histological grade. However, the specific roles of EN2 in CCRCC have yet to be elucidated. In the present study, we examined the effects of inhibiting EN2 expression by human renal tubular epithelial cells (HK-2) and overexpressing EN2 by human clear-cell renal cells (786-O). Results showed that EN2 inhibition accelerated HK-2 cell proliferation, shortened the cell cycle, reduced apoptosis, and acted more invasively. By contrast, EN2 overexpression in 786-O cells decelerated the proliferative ability of 786-O, increased the percentage of cell apoptosis, and weakened the invasive ability. Overall, the results demonstrated that EN2 might play an anti-oncogenic role in oncogenesis and development of CCRCC, thereby maintaining the normal growth of human renal tubular epithelial cells.
Similar content being viewed by others
Abbreviations
- CCRCC:
-
Clear cell renal cell carcinoma
- EN2:
-
Engrailed 2
- RT-qPCR:
-
Real-time quantitative polymerase chain reaction
- IHC:
-
Immunohistochemistry
- HOX:
-
Homeobox
References
Abate-Shen C (2002) Deregulated homeobox gene expression in cancer: cause or consequence. Nat Rev Cancer 2(10):777–785
Chen H, Zhang H, Lee J et al (2007) HOXAS acts directly downstream of retinoic acid receptor beta and contributes to retinoic acid-induced apoptosis and growth inhibition. Cancer Res 67(17):8007–8013
Choyke PL, Glenn GM, Walther MM et al (1995) Von Hippel–Lindau disease: genetic, clinical, and imaging features. Radiology 194(3):629–642
Economides KD, Capecchi MR (2003) Hoxb13 is required for normal differentiation and secretory function of the ventral prostate. Development 130(10):2061–2069
Guan R, Xu Y, Lei H, Gao Z, Xin Z, Guo Y (2014) A novel protein is lower expressed in renal cell carcinoma. Int J Mol Sci 15(5):7398–7408
Joliot A, Maize A, Rosenberg D et al (1998) Identification of a signal sequence necessary for the unconventional secretion of Engrailed meoprotein. Curr Biol 8:856–863
Jung C, Kim RS, Lee SJ et al (2004) HOXB 13 homeodomain protein suppresses the growth of prostate cancer cells by the negative regulation of T cell factor 4. Cancer Res 64(9):3046–3051
Lai Cai-yong, Pan Bin, Luo Yun et al (2014) Engrailed-2 is downregulated but also ectopically expressed in clear cell renal cell carcinoma. Mol Biol Rep 41(6):3651–3657
Ljungberg B, Campbell SC, Cho HY et al (2011) The epidemiology of renal cell carcinoma. Eur Uro 60:615–621
Maizel A, Tassetto M, Filhol O et al (2002) Engrailed homeoprotein secretion is a regulated process. Development. 129(15):3545–3553
Martin NL, Saba-El-Leil MK, Sadekova S et al (2005) EN2 is a candidate oncogene in human breast cancer. Oncogene 24:6890–6901
McGrath SE, Michael A, Morgan R et al (2015) EN2 in prostate cancer. Adv Clin Chem 71:47–76
Miao J, Wang Z, Provencher I-I et al (2007) HOXB 13 promotes ovarian cancer progression. Proc Natl Acad Sci USA 104(43):17093–17098
Morgan R (2006) Engrailed: complexity and economy of a multi-functional transcription factor. FEBS Lett 580(11):2531–2533
Morgan RM, Ismail M, Boxall A et al (2011) Engrailed-2(EN2): a highly specific urinary biomarker for the early diagnosis of prostate cancer. Cancer Res 17:1090–1098
Morgan R, Bryan RT, Javed S et al (2013) Expression of Engrailed-2 (EN2) protein in bladder cancer and its potential utility as a urinary diagnostic biomarker. Eur J Cancer 49(9):2214–2222
Pandha H, Sorensen KD, Orntoft TF et al (2012) Urinary engrailed-2 (EN2) levels predict tumour volume in men undergoing radical prostatectomy for prostate cancer. BJU Int 110(6):287–292
PDQ Cancer Genetics Editorial Board. Genetics of kidney cancer (Renal Cell Cancer). PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002–2015 Oct 1
Shi X, Jiang J, Ye X, Liu Y, Wu Q, Wang L (2014) Prognostic prediction and diagnostic role of intercellular adhesion molecule-1 (ICAM1) expression in clear cell renal cell carcinoma. J Mol Histol 45(4):427–434
Wang Z, Dahiya S, Provencher H et al (2007) The prognostic biomarkers HOXB13, IL17BR, and CHDH are regulated by estrogen in breast cancer. Clin Cancer Res 13(21):6327–6334
Wu X, Chen H, Parker B et al (2006) HOXB7, a homeodomain protein, is overexpressed in breast cancer and confers epithelial-mesenchymal transition. Cancer Res 66(19):9527–9534
Wu X, Lin Y, Shi L, Huang Y, Lai C, Wang Y, Zhang M, Wang S, Heng B, Yu G, Du X, Fang L, Fu Y, Chen J, Guo Z, Su Z, Wu S (2015) Upregulation of centromere protein H is associated with progression of renal cell carcinoma. J Mol Histol 46(4–5):377–385
Yixin Zeng (1999) Oncology [M]. People’s Medical Publishing House, Beijing, pp 96–101
Zhai Y, Kuick R, Nan B et al (2007) Gene expression analysis of preinvasive and invasive cervical squamous cell carcinomas identifies HOXC 10 as a key mediator of invasion. Cancer Res 67(21):10163–10172
Acknowledgments
This study was supported by the Gegion Fund of the National Natural Science Foundation of China (No. 81460386), General program of the Natural Science Foundation of Jiangxi (No. 20151BAB205014), and General program of the Medical Science Research Foundation of Guangdong (No. WSTJJ20140120362301197704250517).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lai, Cy., Xu, Y., Yu, Gs. et al. Engrailed-2 might play an anti-oncogenic role in clear-cell renal cell carcinoma. J Mol Hist 47, 229–237 (2016). https://doi.org/10.1007/s10735-016-9665-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10735-016-9665-4