Overexpression of tumour suppressor retinoblastoma 2 protein (pRb2/p130) in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most common malignancies in Southeast Asia. Although inactivation of pRb2/p130 has been reported in a variety of human cancers, its function in HCC has not been established. In this study we report that loss of expression of pRb2/p130 was detected by immunohistochemistry and western blotting in 15.2% (7 of 46) HCCs examined. High levels of pRb2/p130 expression were found in 84.8% (39 of 46) HCCs studied. Western blot analysis revealed that HCC had 3.5-fold higher pRb2/p130 than adjacent benign liver (ABL) tissues. 71.7% (33 of 46) of HCCs examined exhibited both nuclear and cytoplasmic staining for pRb2/p130. Cytoplasmic staining was found in 93.5% (43 of 46) of ABL tissues. Overproduction of pRb2/p130 in HepG2 cells led to growth suppression, cell cycle arrest in G0/G1, altered cell morphology, inhibition of in vitro colony formation and reduction in tumourigenicity in SCID mice. This demonstration suggests a role of pRb2/p130 as a tumour suppressor protein in HCC and the loss of this protein may lead to the development or progression of HCC. Overexpression of pRb2/p130 in HCC was, therefore, suggested to be a programmed protective response of the organism to uncontrolled proliferation.
Huynh
Hung
H
Laboratory of Molecular Endocrinology, Division of Cellular and Molecular Research, National Cancer Centre of Singapore, Singapore 169610. cmrhth@nccs.com.sg
D000362:Agar / Q000737:chemistry; D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002453:Cell Cycle; D002455:Cell Division; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D018450:Disease Progression; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D016193:G1 Phase; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism; D011233:Precipitin Tests; D014176:Protein Biosynthesis; D011506:Proteins; D016192:Resting Phase, Cell Cycle; D050717:Retinoblastoma-Like Protein p130; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D011506:Proteins; C493837:RBL2 protein, human; C493838:Rbl2 protein, mouse; D050717:Retinoblastoma-Like Protein p130; D000362:Agar