TFE3 regulates renal adenocarcinoma cell proliferation via activation of the mTOR pathway

Fang,Yuan; Bao,Wei; Rao,Qiu; Wang,Xuan; Xia,Qiuyuan; Shen,Qin; Zhou,Xiaojun; Yao,Bing

doi:10.3892/mmr.2017.6930

TFE3 regulates renal adenocarcinoma cell proliferation via activation of the mTOR pathway

Authors:
- Yuan Fang
- Wei Bao
- Qiu Rao
- Xuan Wang
- Qiuyuan Xia
- Qin Shen
- Xiaojun Zhou
- Bing Yao
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Affiliations: Reproductive Medical Center, Jinling Hospital, Clinical Medical School of Southern Medical University, Nanjing, Jiangsu 210002, P.R. China, Department of Pathology, Jinling Hospital, Clinical Medical School of Southern Medical University, Nanjing, Jiangsu 210002, P.R. China
Published online on: July 5, 2017 https://doi.org/10.3892/mmr.2017.6930
Pages: 2721-2725
Copyright: © Fang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the role of transcription factor E3 (TFE3) in the regulation of proliferation in renal adenocarcinoma cells. The LV‑TFE3 overexpression (OE) lentivirus and negative control CON195 (NC) lentivirus were transfected into the ACHN cell line. Protein expression of FLAG‑tag TFE3 was determined using western blot analysis. Differences in cell proliferation, plate clone formation and cell cycle distribution between OE and NC groups were compared using MTT, plate colony formation and flow cytometry assays, respectively. The levels of mammalian target of rapamycin (mTOR) and phosphorylated ribosomal protein S6 (p‑rpS6) were analyzed by western blotting. Cell proliferation and colony formation increased significantly in the OE group compared with the NC group. The % of cells in the G1 and G2 phases of the cell cycle decreased, while the % of cells in the S phase of the cell cycle increased in the OE group compared with the NC group. In addition, mTOR and p‑rpS6 levels were increased in the OE group compared with the NC group. The results of the present study demonstrated that TFE3 overexpression resulted in increased ACHN cell proliferation and plate clone formation. TFE3 may promote renal tumor growth by regulating cell cycle progression and activating the phosphatidylinositol 3‑kinase/AKT serine/threonine kinase 1/mTOR signaling pathway.

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1	Ramphal R, Pappo A, Zielenska M, Grant R and Ngan BY: Pediatric renal cell carcinoma: Clinical, pathologic, and molecular abnormalities associated with the members of the mit transcription factor family. Am J Clin Pathol. 126:349–364. 2006. View Article : Google Scholar : PubMed/NCBI
2	Komai Y, Fujiwara M, Fujii Y, Mukai H, Yonese J, Kawakami S, Yamamoto S, Migita T, Ishikawa Y, Kurata M, et al: Adult Xp11 translocation renal cell carcinoma diagnosed by cytogenetics and immunohistochemistry. Clin Cancer Res. 15:1170–1176. 2009. View Article : Google Scholar : PubMed/NCBI
3	Lopez-Beltran A, Cheng L, Vidal A, Scarpelli M, Kirkali Z, Blanca A and Montironi R: Pathology of renal cell carcinoma: An update. Anal Quant Cytopathol Histpathol. 35:61–76. 2013.PubMed/NCBI
4	Argani P, Lal P, Hutchinson B, Lui MY, Reuter VE and Ladanyi M: Aberrant nuclear immunoreactivity for TFE3 in neoplasms with TFE3 gene fusions: A sensitive and specific immunohistochemical assay. Am J Surg Pathol. 27:750–761. 2003. View Article : Google Scholar : PubMed/NCBI
5	Argani P, Antonescu CR, Illei PB, Lui MY, Timmons CF, Newbury R, Reuter VE, Garvin AJ, Perez-Atayde AR, Fletcher JA, et al: Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma: A distinctive tumor entity previously included among renal cell carcinomas of children and adolescents. Am J Pathol. 159:179–192. 2001. View Article : Google Scholar : PubMed/NCBI
6	Argani P, Olgac S, Tickoo SK, Goldfischer M, Moch H, Chan DY, Eble JN, Bonsib SM, Jimeno M, Lloreta J, et al: Xp11 translocation renal cell carcinoma in adults: Expanded clinical, pathologic, and genetic spectrum. Am J Surg Pathol. 31:1149–1160. 2007. View Article : Google Scholar : PubMed/NCBI
7	Castellvi J, Garcia A, Ruiz-Marcellan C, Hernández-Losa J, Peg V, Salcedo M, Gil-Moreno A, Ramon Y and Cajal S: Cell signaling in endometrial carcinoma: Phosphorylated 4E-binding protein-1 expression in endometrial cancer correlates with aggressive tumors and prognosis. Hum Pathol. 40:1418–1426. 2009. View Article : Google Scholar : PubMed/NCBI
8	Parikh J, Coleman T, Messias N and Brown J: Temsirolimus in the treatment of renal cell carcinoma associated with Xp11.2 translocation/TFE gene fusion proteins: A case report and review of literature. Rare Tumors. 1:e532009.PubMed/NCBI
9	Choueiri TK, Lim ZD, Hirsch MS, Tamboli P, Jonasch E, McDermott DF, Dal Cin P, Corn P, Vaishampayan U, Heng DY and Tannir NM: Vascular endothelial growth factor-targeted therapy for the treatment of adult metastatic Xp11.2 translocation renal cell carcinoma. Cancer. 116:5219–5225. 2010. View Article : Google Scholar : PubMed/NCBI
10	Rao Q, Williamson SR, Zhang S, Eble JN, Grignon DJ, Wang M, Zhou XJ, Huang W, Tan PH, Maclennan GT and Cheng L: TFE3 break-apart FISH has a higher sensitivity for Xp11.2 translocation-associated renal cell carcinoma compared with TFE3 or cathepsin K immunohistochemical staining alone: Expanding the morphologic spectrum. Am J Surg Pathol. 37:804–815. 2013. View Article : Google Scholar : PubMed/NCBI
11	Dickson BC, Brooks JS, Pasha TL and Zhang PJ: TFE3 expression in tumors of the microphthalmia-associated transcription factor (MiTF) family. Int J Surg Pathol. 19:26–30. 2011. View Article : Google Scholar : PubMed/NCBI
12	Rao Q, Guan B and Zhou XJ: Xp11.2 Translocation renal cell carcinomas have a poorer prognosis than non-Xp11.2 translocation carcinomas in children and young adults: A meta-analysis. Int J Surg Pathol. 18:458–464. 2010. View Article : Google Scholar : PubMed/NCBI
13	Xu L, Yang R, Gan W, Chen X, Qiu X, Fu K, Huang J, Zhu G and Guo H: Xp11.2 translocation renal cell carcinomas in young adults. BMC Urol. 15:572015. View Article : Google Scholar : PubMed/NCBI
14	Ploper D and De Robertis EM: The MITF family of transcription factors: Role in endolysosomal biogenesis, Wnt signaling, and oncogenesis. Pharmacol Res. 99:36–43. 2015. View Article : Google Scholar : PubMed/NCBI
15	Giangrande PH, Hallstrom TC, Tunyaplin C, Calame K and Nevins JR: Identification of E-Box factor TFE3 as a functional partner for the E2F3 transcription factor. Mol Cell Biol. 23:3707–3720. 2003. View Article : Google Scholar : PubMed/NCBI
16	Leone G, Degregori J, Yan Z, Jakoi L, Ishida S, Williams RS and Nevins JR: E2F3 activity is regulated during the cell cycle and is required for the induction of S phase. Genes Dev. 12:2120–2130. 1998. View Article : Google Scholar : PubMed/NCBI
17	Li M, Wang Y, Yu Y, Nishizawa M, Nakajima T, Ito S and Kannan P: The human transcription factor activation protein-2 gamma (AP-2gamma): Gene structure, promoter and, expression in mammary carcinoma cell lines. Gene. 301:43–51. 2002. View Article : Google Scholar : PubMed/NCBI
18	Yu Y, Wang Y, Li M and Kannan P: Tumorigenic effect of transcription factor hAP-2alpha and the intricate link between hAP-2alpha activation and squelching. Mol Carcinog. 34:172–179. 2002. View Article : Google Scholar : PubMed/NCBI
19	Furuya N, Kamai T, Shirataki H, Yanai Y, Fukuda T, Mizuno T, Nakamura F, Kambara T, Nakanishi K, Abe H and Yoshida K: Serum interferon alpha receptor 2 mRNA may predict efficacy of interferon alpha with/without low-dose sorafenib for metastatic clear cell renal cell carcinoma. Cancer Immunol Immunother. 60:793–808. 2011. View Article : Google Scholar : PubMed/NCBI
20	Kamai T, Tsujii T, Arai K, Takagi K, Asami H, Ito Y and Oshima H: Significant association of Rho/ROCK pathway with invasion and metastasis of bladder cancer. Clin Cancer Res. 9:2632–2641. 2003.PubMed/NCBI
21	Pantuck AJ, Seligson DB, Klatte T, Yu H, Leppert JT, Moore L, O'Toole T, Gibbons J, Belldegrun AS and Figlin RA: Prognostic relevance of the mTOR pathway in renal cell carcinoma: Implications for molecular patient selection for targeted therapy. Cancer. 109:2257–2267. 2007. View Article : Google Scholar : PubMed/NCBI
22	Argani P, Hicks J, De Marzo AM, Albadine R, Illei PB, Ladanyi M, Reuter VE and Netto GJ: Xp11 translocation renal cell carcinoma (RCC): Extended immunohistochemical profile emphasizing novel RCC Markers. Am J Surg Pathol. 34:1295–1303. 2010. View Article : Google Scholar : PubMed/NCBI