Philippe J, Chick W L, Habener J F
J Clin Invest. 1987 Feb;79(2):351-8. doi: 10.1172/JCI112819.
The developmental origin of the four phenotypically distinct hormone-producing islet cells (insulin, glucagon, somatostatin, pancreatic polypeptide) is unclear. To investigate the potential for phenotypic differentiation of islet cells, we prepared several clonal cell lines from a radiation-induced rat islet tumor and analyzed them for insulin, glucagon, and somatostatin gene expression by cDNA hybridization, immunocytochemistry, and radioimmunoassay. We found expression of all three genes in the tumor and in the parental cell line and mixed variable phenotypes in the clonal lines derived from the parental line. We also observed the ectopic expression of the angiotensinogen gene in the tumor and the cell lines. The relative levels of hormonal gene expression differed among the cell lines but remained fixed during continuous passage. The three islet hormone mRNAs were larger compared to the pancreas owing to longer poly(A) tracts. These observations indicate that neoplastic islet cells retain the potential to differentiate into hormone-specific cellular phenotypes and may mimic developmental pathways of the pancreatic islets.
四种表型不同的产生激素的胰岛细胞（胰岛素、胰高血糖素、生长抑素、胰多肽）的发育起源尚不清楚。为了研究胰岛细胞表型分化的潜能，我们从辐射诱导的大鼠胰岛肿瘤中制备了几种克隆细胞系，并通过cDNA杂交、免疫细胞化学和放射免疫测定分析它们的胰岛素、胰高血糖素和生长抑素基因表达。我们在肿瘤和亲本细胞系中发现了所有这三个基因的表达，并且在源自亲本系的克隆系中发现了混合的可变表型。我们还观察到血管紧张素原基因在肿瘤和细胞系中的异位表达。激素基因表达的相对水平在不同细胞系中有所不同，但在连续传代过程中保持固定。与胰腺相比，三种胰岛激素mRNA由于多聚腺苷酸序列更长而更大。这些观察结果表明，肿瘤性胰岛细胞保留了分化为激素特异性细胞表型的潜能，并且可能模拟胰岛的发育途径。
