RASSF1A expression inhibits the growth of hepatocellular carcinoma from Qidong County

• Published in: Journal of gastroenterology and hepatology Vol. 23; no. 9; pp. 1448 - 1458
• Main Authors: Xue, Wan-Jiang, Li, Chun, Zhou, Xiao-Jun, Guan, Hong-Geng, Qin, Lei, Li, Peng, Wang, Zhi-Wei, Qian, Hai-Xin
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Publishing Asia 01.09.2008; Blackwell Science
• Subjects: Adult; Animals; Antibiotics, Antineoplastic - pharmacology; apoptosis; Biological and medical sciences; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - virology; Cell Cycle; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; China; cyclin D1; Cyclin D1 - metabolism; DNA Replication; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation, Neoplastic; Hepatitis B - complications; Hepatitis B - immunology; Hepatitis B Surface Antigens - metabolism; Hepatitis B virus; hepatocarcinogenesis; Humans; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Liver Neoplasms - virology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Logistic Models; Male; Medical sciences; Mice; Mice, Nude; mitomycin; Mitomycin - pharmacology; Mutation; Odds Ratio; Risk Assessment; Risk Factors; Time Factors; Transfection; tumor suppressor; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumors; Xenograft Model Antitumor Assays; China; Antineoplastic agent; Mitomycin; Growth; Hepatic disease; Hepatocellular carcinoma; tumor suppressor; Malignant tumor; hepatocarcinogenesis; Cyclin D1; Carcinogenesis; Liver cancer; Alkylating agent; Antibiotic; Gastroenterology; Digestive diseases; Suppressor; Cancer; Apoptosis
• ISSN: 0815-9319; 1440-1746
• DOI: 10.1111/j.1440-1746.2007.05067.x

Background and Aim:  The tumor‐suppressing role of Ras‐association domain family 1A (RASSF1A) has been described in several systems. In this study, we tested its tumor‐suppressing ability and the potential molecular mechanisms in hepatocellular carcinoma (HCC) from Qidong County. Methods:  Reverse transcription polymerase chain reaction and Northern blotting were employed to detect the expression of RASSF1A in HCC. After establishing stable RASSF1A (wild type or mutant) expressing ‘qi dong gan ai yan jiu suo’ ([Qidong Institute of Liver Cancer] QGY)‐7703 cell lines, we tested the effects of RASSF1A expression on cell growth by cell proliferation rate, cell colony formation, and cell cycle progression. We also tested the effects of RASSF1A expression on tumorigenesis in nude mice and on cellular sensitivity to mitomycin treatment. Results:  The RASSF1A transcript was not found in 75% (three of four) of HCC cell lines and 67% (32/48) of HCC primary biopsies. The stepwise regression analyses indicated that the loss of RASSF1A expression was more frequent in patients who were hepatitis B virus surface antigen positive (HBsAg+) compared to those who were HBsAg(−), both in tumor and corresponding non‐cancerous tissues. The wild‐type (wt)‐RASSF1A expression in the QGY‐7703 cell line resulted in fewer and smaller clones, decreased xenograft tumor volume and weight, and G1/S arrest in vitro and in vivo. The wt‐RASSF1A expression also decreased the cyclin D1 protein expression, which appeared to be at the level of post‐transcriptional control. In addition, the wt‐RASSF1A expression increased cell growth inhibition and the percentage of cells with sub‐G1 DNA content when the cells were treated with mitomycin. Conclusion:  RASSF1A is a tumor suppressor in HCC. The loss of RASSF1A expression may be related to HBsAg+ in hepatocarcinogenesis. Its inactivation may play an important role in the development of HCC.