Comparative phenotypic studies of duct epithelial cell lines derived from normal human pancreas and pancreatic carcinoma
Comparative phenotypic studies of duct epithelial cell lines derived from normal human pancreas and pancreatic carcinoma
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DOI：
10.1016/s0002-9440(10)65567-8
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发表时间：
1998-07-01
影响因子：
6
通讯作者：
Tsao, MS
中科院分区：
文献类型：
--
作者：
Liu, N;Furukawa, T;Tsao, MS
我们研究了正常人胰管上皮 (HPDE) 细胞系中几种酪氨酸激酶受体、生长因子和 p16(INK4A) 细胞周期蛋白抑制剂的 mRNA/蛋白表达，并将其与五种胰腺导管癌细胞系进行比较。培养的 HPDE 细胞表达低水平的表皮生长因子受体 (EGFR)、erbB2、转化生长因子 (TGF)-α、Met/肝细胞生长因子受体 (HGFR)、血管内皮生长因子（VEGF）和角质形成细胞生长因子（KGF），它们还表达高水平的双调蛋白，但不表达EGF和cripto。原代正常HPDE细胞和表达转染人乳头状瘤病毒16的EbE7基因的细胞中的表达水平相似，但它们的永生化似乎增强了EGFR和Met/HGFR的表达，相比之下，胰腺癌细胞系通常表现出EGFR、erbB2、TGF-α、Met/HGFR、VEGF和KGF的过度表达，但它们始终表现出双调蛋白mRNA表达的显着下调，与所有癌细胞相比在显示 p16 基因缺失的细胞系中，HPDE 细胞始终表现出正常的 p16 基因型及其 mRNA 表达。这是第一份将培养的胰腺导管癌细胞的表型表达与源自正常人胰管的上皮细胞系进行比较的报告。研究结果证实，人胰管细胞的恶性转化通常会导致各种生长因子和受体的表达失调。
We have investigated the mRNA/protein expression of several tyrosine kinase receptors, growth factors, and p16(INK4A) cyclin inhibitor in cell lines derived from normal human pancreatic duct epithelium (HPDE) and compared them with those of five pancreatic ductal carcinoma cell lines, Cultured HPDE cells express low levels of epidermal growth factor receptor (EGFR), erbB2, transforming growth factor (TGF)-alpha, Met/hepatocyte growth factor receptor (HGFR), vascular endothelial growth factor (VEGF), and keratinocyte growth factor (KGF), They also expressed high levels of amphiregulin but did not express EGF and cripto. The expression levels were similar in primary normal HPDE cells and those expressing transfected EbE7 genes of human papilloma virus-16, but their immortalization appeared to enhance the expression of EGFR and Met/HGFR, In comparison, pancreatic carcinoma cell Lines commonly demonstrated overexpression of EGFR, erbB2, TGF-alpha, Met/HGFR, VEGF, and KGF, but they consistently showed marked down-regulation of amphiregulin mRNA expression, In contrast to all carcinoma cell lines that showed deletions of the p16 gene, HPDE cells consistently demonstrated normal p16 genotype and its mRNA expression, This is the first report that compares the phenotypic expression of cultured pancreatic ductal carcinoma cells with epithelial cell lines derived from normal human pancreatic ducts, The findings confirm that malignant transformation of human pancreatic duct cells commonly results in a deregulation of expression of various growth factors and receptors.