Satonaka K, Nakamura T, Maeda S
Second Department of Pathology, Kobe University School of Medicine.
Kobe J Med Sci. 1992 Jun;38(3):191-203.
Current evidence suggests that a multipotential endodermal cell may give rise to all islet cell phenotypes. Five (N1-N5) and twenty-one (m1-m21) pluripotent rat islet cell clones were isolated from two hormone-producing cell line (RIN-r, RINm5F) derived from a radiation-induced islet tumor. To investigate the characteristics of these clones, we analyzed the hormone expression and secretion by Northern blot, immunocytochemistry, and radioimmunoassay. Increased expression and secretion of insulin and glucagon were observed in these clones. The present examination might also be proof of the secretion of both insulin and glucagon in the single cell of the m21 clone isolated from RINm5F. These cell lines also overexpress the Ha-ras proto-oncogene. In order to determine whether or not the overexpression was caused by gene translocation, the insulin and Ha-ras gene loci in N3 isolated from RIN-r were assigned by in situ hybridization. Both of the genes were located on the long arm of chromosome 1, but no gene translocation was observed. These findings suggest that the expression of insulin and Ha-ras is not affected by chromosomal translocation, but it may be functionally linked in these clones. Overexpression of these three genes may indicate that these clones have the same characteristics as the embryonic immature islet cell.
目前的证据表明,一种多能性内胚层细胞可能产生所有胰岛细胞表型。从源自辐射诱导的胰岛肿瘤的两种激素产生细胞系(RIN-r、RINm5F)中分离出五个(N1-N5)和二十一个(m1-m21)多能性大鼠胰岛细胞克隆。为了研究这些克隆的特征,我们通过Northern印迹、免疫细胞化学和放射免疫测定分析了激素的表达和分泌。在这些克隆中观察到胰岛素和胰高血糖素的表达和分泌增加。本研究也可能证明从RINm5F分离出的m21克隆的单个细胞中同时分泌胰岛素和胰高血糖素。这些细胞系还过度表达Ha-ras原癌基因。为了确定这种过度表达是否由基因易位引起,通过原位杂交确定了从RIN-r分离出的N3中的胰岛素和Ha-ras基因座。这两个基因都位于1号染色体的长臂上,但未观察到基因易位。这些发现表明,胰岛素和Ha-ras的表达不受染色体易位的影响,但在这些克隆中它们可能在功能上相关联。这三个基因的过度表达可能表明这些克隆具有与胚胎未成熟胰岛细胞相同的特征。