ANALYSIS OF CELLULAR AND GENETIC ALTERATIONS DURING HEPATOCARCINOGENESIS

肝细胞癌是亚洲最常见的癌症之一。 还有非洲。来自该实验室和其他实验室的最新证据表明 表明16号染色体上的等位基因缺失在 HCCS来自启东省中国，但不是来自北京。其中 信息丰富的启东样本中，90%表现出杂合性缺失(LOH) 在TAT标记基因座(染色体位置16q22)，58%的人表现为LOH 在DD16S7基因座(16q22-24)。这类删除通常与 肿瘤抑制基因缺失。我们正在通过以下方式扩展这些研究 检查了来自启东和北京的更大一组样本，并通过 专注于染色体长臂(或“Q”臂)特有的标记 16.研究转化生长因子-β1(TGF-β1)的作用 β1)在肝癌发生中的作用及可能的逃逸机制(S) 转化生长因子-β1、转化生长因子-β1抑制肿瘤细胞生长 54例人肝癌及其周围组织的产生 对非肿瘤性肝组织进行原位杂交和 免疫组织化学。特别是，进行了评估 胰岛素样生长因子II受体(IGF II R)的潜在作用 和转化生长因子-βII型受体中丝裂原抑制作用的丧失 在肿瘤里。结果证实并补充到了增加的正文中 数据表明转化生长因子-β1在血管生成过程中的重要作用 肝纤维化/-肝硬变。然而，肝细胞是主要的 转化生长因子-β1在肿瘤和纤维化肝脏中的来源及结果 与大多数肝纤维化模型不同。转化生长因子-β1 转录本在90%的癌组织中表达。免疫组织化学 转化生长因子-β1的染色通常与原位数据有良好的相关性， 但在七个表达转录本的肿瘤中没有检测到蛋白质。 所有研究的肝细胞癌都表达高水平的 II转化生长因子-β受体基因。IGF II R的转录产物不是 在56%的肿瘤中被检测到。

Hepatocellular carcinoma (HCC) is one of the most common cancers in Asia and Africa. Recent evidence from this laboratory and others has indicated that allelic losses on chromosome 16 are especially common in HCCs from the Qidong province of China, though not from Beijing. Among the informative Qidong samples, 90% showed loss of heterozygosity (LOH) at the TAT marker locus (chromosome location 16q22) and 58% showed LOH at the DD16S7 locus (16q22-24). Such deletions are often associated with loss of a tumor suppressor gene. We are extending these studies by examining a larger set of samples from Qidong and Beijing, and by concentrating on markers specific to the long (or "q") arm of chromosome 16. To study the involvement of transforming growth factor beta 1 (TGF- beta1) in liver carcinogenesis and the possible escape mechanism(s) of the tumor cells from the growth inhibition of TGF-beta1, TGF-beta1 production in 54 human liver carcinomas and in the surrounding nontumorous liver tissue was analyzed by in situ hybridization and immunohistochemistry. In particular, attempts were undertaken to assess the potential role of insulin-like growth factor II receptor (IGF II R) and TGF-beta type II receptor in the loss of the mitoinhibitory effects in the tumors. The results confirmed and added to the increasing body of data indicating a significant role for TGF-beta1 in the process of hepatic fibrosis/-cirrhosis. However, the hepatocytes were the major source of TGF-beta1 in the tumored and fibrotic livers and this result is different from most of the hepatic fibrosis models. TGF-beta1 transcripts were expressed in 90% of the carcinomas. Immunohistochemical staining for TGF-beta1 generally correlated well with the in situ data, but no protein was detected in seven tumors expressing the transcripts. All the studied hepatocellular carcinomas expressed high levels of type II TGF-beta receptor mRNA. The transcripts for IGF II R were not detected in 56% of the tumors.