Original Article
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. May 21, 2013; 19(19): 2913-2920
Published online May 21, 2013. doi: 10.3748/wjg.v19.i19.2913
Overexpression of p42.3 promotes cell growth and tumorigenicity in hepatocellular carcinoma
Wei Sun, Wei-Wei Dong, Lin-Lin Mao, Wen-Mei Li, Jian-Tao Cui, Rui Xing, You-Yong Lu
Wei Sun, Wen-Mei Li, Jian-Tao Cui, Rui Xing, You-Yong Lu, Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital/Institute, Beijing 100142, China
Wei-Wei Dong, Department of Medical Oncology, The General Hospital of Chinese People’s Liberation Army, Beijing 100853, China
Lin-Lin Mao, Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China
Author contributions: Sun W and Dong WW conducted the experiments, analysed data and prepared figures and manuscript; Mao LL, Li WM and Cui JT performed experiments and analyzed data in vitro and in vivo; Xing R and Lu YY supervised experimental work; all authors read the manuscript and approved its submission.
Supported by The Beijing Natural Science foundation, No. 5102018; National Bio-Tech 86-3, No. 2006AA02A402 and No. 2012AA02A504
Correspondence to: Rui Xing, PhD, Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital/Institute, No. 52 Fucheng Road, Haidian District, Beijing 100142, China. sherry19820420@hotmail.com
Telephone: +86-10-88196731 Fax: +86-10-88122437
Received: January 20, 2013
Revised: April 2, 2013
Accepted: April 9, 2013
Published online: May 21, 2013

AIM: To investigate the association of p42.3 expression with clinicopathological characteristics and the biological function of p42.3 in human hepatocellular carcinoma (HCC).

METHODS: We used reverse transcription-polymerase chain reaction (RT-PCR), quantitative real-time RT-PCR and western blotting to detect p42.3 mRNA and protein expression in hepatic cell lines. We examined primary HCC samples and matched adjacent normal tissue by immunohistochemistry to investigate the correlation between p42.3 expression and clinicopathological features. HepG2 cells were transfected with a pIRES2-EGFP-p42.3 expression vector to examine the function of the p42.3 gene. Transfected cells were analyzed for their viability and malignant transformation abilities by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation assay, and tumorigenicity assay in nude mice.

RESULTS: p42.3 is differentially expressed in primary HCC tumors and cell lines. Approximately 69.6% (96/138) of cells were p42.3-positive in hepatic tumor tissues, while 30.7% (35/114) were p42.3-positive in tumor-adjacent normal tissues. Clinicopathological characteristics of the HCC specimens revealed a significant correlation between p42.3 expression and tumor differentiation (P = 0.031). However, p42.3 positivity was not related to tumor tumor-node-metastasis classification, hepatitis B virus status, or hepatoma type. Regarding p42.3 overexpression in stably transfected HepG2 cells, we discovered significant enhancement of cancer cell growth and colony formation in vitro, and significantly enhanced tumorigenicity in nude mice. Western blot analysis of cell cycle proteins revealed that enhanced p42.3 levels promote upregulation of proliferating cell nuclear antigen, cyclin B1 and mitotic arrest deficient 2.

CONCLUSION: p42.3 promotes tumorigenicity and tumor growth in HCC and may be a potential target for future clinical cancer therapeutics.

Keywords: p42.3, Hepatocellular carcinoma, HepG2, Overexpression, Tumorigenicity

Core tip: p42.3 is a novel tumor-specific and mitosis phase-dependent expression gene. It is believed to be involved in tumorigenesis in gastric and colorectal cancer. To the best of our knowledge, this is the first study to investigate the expression and function of p42.3 in hepatocellular carcinoma (HCC). We found that p42.3 promotes tumorigenicity and tumor growth in HepG2 cells and is overexpressed in HCC. These results suggest that p42.3 may act as a novel tumor biomarker and aid in the development of improved therapeutic strategies.