Expression of FOXJ1 in hepatocellular carcinoma: Correlation with patients' prognosis and tumor cell proliferation

Molecular Carcinogenesis - Tập 52 Số 8 - Trang 647-659 - 2013
Hongwei Chen1,2, Xiaodong Huang2, Hong‐Chen Li1, Song He3, Runzhou Ni2, Cui‐Hua Chen2, Peng Chen2, Gang Wu2, Guihua Wang2, Yingying Wang2, Yunhong Zhao2, Yixin Zhang3, Aiguo Shen4,3,5, Huimin Wang4,5,2
1Clinical Laboratory, The First Hospital of Qinhuangdao, Hebei Province, P.R. China
2Medical Laboratory Center, Affiliated Hospital of Nantong University, Jiangsu Province, P.R. China
3Department of Pathology, Affiliated Cancer Hospital of Nantong University, Jiangsu Province, P.R. China
4Ai-Guo Shen, Department of Pathology, Affiliated Cancer Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, P.R. China.
5Hui-Min Wang, Medical Laboratory Center, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, P.R. China.

Tóm tắt

AbstractFOXJ1 is a member of the forkhead box (FOX) family of transcription factors. Recent studies suggested that FOXJ1 may function as a tumor suppressor gene in breast cancer. To investigate the potential roles of FOXJ1 in hepatocellular carcinoma (HCC), expression of FOXJ1 was first examined in eight paired frozen HCC and adjacent noncancerous liver tissues by Western blot, and we found that FOXJ1 was upregulated in HCC specimens. In addition, immunohistochemistry was performed to confirm our results in 108 HCC samples. Moreover, we also evaluated its relation with clinicopathological variables and the prognostic significance. The data showed that high expression of FOXJ1 was associated with histological grade (P < 0.001), and FOXJ1 was positively correlated with proliferation marker Ki‐67 (P < 0.01). Univariate analysis suggested that FOXJ1 expression was associated with poor prognosis (P < 0.001). Multivariate analysis indicated that tumor grade (P < 0.0001), metastasis (P = 0.0451), tumor size (P = 0.0459), FOXJ1 (P = 0.0011), and Ki‐67 (P = 0.0006) were independent prognostic markers for HCC. Furthermore, we noted that there existed the change of the level of FOXJ1 subcellular localization during cell‐cycle transition in HepG2 cells by immunofluorescence and cell fractionation. Besides, we employed FOXJ1 overexpression/knockdown approaches to investigate the effects of FOXJ1 on HCC cell proliferation and cell‐cycle distribution and found that overexpression of FOXJ1 can promote tumor cell proliferation and cell‐cycle transition. Our results suggested that FOXJ1 was overexpressed in HCCs and associated with histological grade and poor prognosis. Overexpression of FOXJ1 was also involved in tumor cell proliferation and cell‐cycle progression in HCC cell lines. © 2012 Wiley Periodicals, Inc.

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Tài liệu tham khảo

10.1016/S0140-6736(03)14964-1

10.1038/nrc2223

10.1186/1479-7364-4-5-345

Lin L, 2002, The hepatocyte nuclear factor 3 alpha gene, HNF3alpha (FOXA1), on chromosome band 14q13 is amplified and overexpressed in esophageal and lung adenocarcinomas, Cancer Res, 62, 5273

10.1158/1078-0432.CCR-08-3155

10.1073/pnas.0703900104

10.1016/j.bbrc.2010.01.015

10.1038/ncb1217

10.1038/ncb0205-108

10.1158/0008-5472.CAN-05-3003

10.1128/MCB.25.24.10875-10894.2005

10.1073/pnas.252570299

10.1002/hep.20375

10.1002/hep.20718

Teh MT, 2002, FOXM1 is a downstream target of Gli1 in basal cell carcinomas, Cancer Res, 62, 4773

10.1158/0008-5472.CAN-04-4059

10.1158/0008-5472.CAN-05-3138

10.1038/sj.onc.1207392

10.1158/0008-5472.CAN-07-1265

10.1002/path.2355

10.1053/j.gastro.2007.01.036

10.1016/S0002-9440(10)63463-3

10.1016/S0092-8674(04)00302-2

10.1016/S0092-8674(04)00452-0

10.1074/jbc.M207509200

10.1016/S0092-8674(04)00298-3

10.1038/ng1193-230

10.1002/gcc.2870110203

10.1038/sj.onc.1210626

10.1210/en.2007-0756

10.1038/onc.2008.24

10.1073/pnas.90.9.3948

10.1073/pnas.92.10.4249

10.1165/ajrcmb.23.1.4070

10.1172/JCI4786

10.4049/jimmunol.175.12.7805

10.4049/jimmunol.175.2.951

10.1242/dev.041129

10.1007/s10038-006-0359-8

10.1038/emm.2007.87

10.1002/gcc.20620

Inagawa S, 2002, Expression and prognostic roles of beta‐catenin in hepatocellular carcinoma: Correlation with tumor progression and postoperative survival, Clin Cancer Res, 8, 450

Xu X, 2003, Overexpression of CDC25A phosphatase is associated with hypergrowth activity and poor prognosis of human hepatocellular carcinomas, Clin Cancer Res, 9, 1764

Bicknell KA, 2005, Forkhead (FOX) transcription factors and the cell cycle: Measurement of DNA binding by FoxO and FoxM transcription factors, Methods Mol Biol, 296, 247

10.1093/carcin/bgr055

10.1002/1097-0142(19930915)72:6<1859::AID-CNCR2820720612>3.0.CO;2-A

10.1016/j.ejca.2007.01.004

10.1038/nrc1934