Aihara T, Noguchi S, Miyoshi Y, Nakano H, Sasaki Y, Nakamura Y, Monden M, Imaoka S
Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.
Hepatology. 1998 Jul;28(1):86-9. doi: 10.1002/hep.510280113.
Allelic imbalance of the insulin-like growth factor II (IGF II) gene expression is often seen in hepatocellular carcinoma (HCC). To investigate the role of allelic imbalance in hepatocarcinogenesis, we have studied allelic expression status of the IGF II gene in dysplastic nodules, which are precancerous lesions of HCC, as well as in HCCs of different histological grade, and the influence of the allelic imbalance on IGF II gene expression has also been examined. Allelic imbalance was observed in 3 of 7 dysplastic nodules, in 7 of 9 well-differentiated HCCs, and in 8 of 9 moderately differentiated HCCs. IGF II gene expression level, which was studied by a semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR), was significantly higher (3.6-fold) in the dysplastic nodules than the control livers, but a significant increase in the IGF II gene expression was not observed in well- and moderately differentiated HCCs as compared with the control livers. These results demonstrate that the allelic imbalance of the IGF II gene expression is seen in the early stage (precancerous lesions) of hepatocarcinogenesis. Association of the allelic imbalance with an increased expression of the IGF II gene in the precancerous lesions might suggest a possible involvement of an IGF II autocrine loop in the pathogenesis of these lesions.
胰岛素样生长因子II（IGF II）基因表达的等位基因失衡在肝细胞癌（HCC）中经常可见。为了研究等位基因失衡在肝癌发生中的作用，我们研究了IGF II基因在发育异常结节（HCC的癌前病变）以及不同组织学分级的HCC中的等位基因表达状态，并检测了等位基因失衡对IGF II基因表达的影响。在7个发育异常结节中有3个观察到等位基因失衡，在9个高分化HCC中有7个，在9个中分化HCC中有8个。通过半定量逆转录聚合酶链反应（RT-PCR）研究的IGF II基因表达水平，在发育异常结节中比对照肝脏显著更高（3.6倍），但与对照肝脏相比，在高分化和中分化HCC中未观察到IGF II基因表达的显著增加。这些结果表明，IGF II基因表达的等位基因失衡在肝癌发生的早期阶段（癌前病变）即可见到。癌前病变中等位基因失衡与IGF II基因表达增加的关联可能提示IGF II自分泌环可能参与了这些病变的发病机制。
