RASSF1A expression inhibits the growth of hepatocellular carcinoma from Qidong County.
OBJECTIVE
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 G(1)/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-G(1) DNA content when the cells were treated with mitomycin.


CONCLUSIONS
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.
Department of General Surgery, the First Affiliated Hospital of Soochow University, Suzhou, China.
Wan-Jiang
WJ
Xue
Chun
C
Li
Xiao-Jun
XJ
Zhou
Hong-Geng
HG
Guan
Lei
L
Qin
Peng
P
Li
Zhi-Wei
ZW
Wang
Hai-Xin
HX
Qian
D000328:Adult; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002681:China; D019938:Cyclin D1 / Q000378:metabolism; D004261:DNA Replication; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006509:Hepatitis B / Q000150:complications / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D016015:Logistic Models; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016685:Mitomycin / Q000494:pharmacology; D009154:Mutation; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
D000903:Antibiotics, Antineoplastic; C530104:CCND1 protein, human; D006514:Hepatitis B Surface Antigens; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D016685:Mitomycin