Changes in gene expression accompanying chemically-induced malignant transformation of human fibroblasts.
Changes in gene expression accompanying chemically-induced malignant transformation of human fibroblasts.
复制标题
伴随化学诱导的人类成纤维细胞恶性转化的基因表达的变化。
作者：
J. Leavitt;D. Goldman;C. Merril;T. Kakunaga
伴随肿瘤转化的基因表达的调节已经通过计算机化的显微光密度测定或通过二维聚丙烯酰胺凝胶电泳分离的[35 S]蛋氨酸标记多肽的放射自显影模式进行了评估。比较了亲本二倍体人成纤维细胞（KD株）和克隆来源的恶性成纤维细胞（HUT-14株）的近1000种多肽种类。HUT-14成纤维细胞在两个功能性β-肌动蛋白基因之一中表达突变，并具有将其区分为肿瘤细胞的特性。在测量的700种更丰富的多肽中，13种丢失，14种在这种肿瘤转化后获得。据估计，少于或等于2%的表达丰富的多肽的基因被激活或关闭，但至少32%的定量调制作为这种肿瘤转化的结果。指定“高度可变”和“边缘可变”多肽的类别。在“高度可变”的多肽中，在KD亲本细胞中几乎检测不到的两种相关物质在转化细胞中以高25-31倍的速率合成，并且纤连蛋白的细胞相关和细胞外基质形式各自减少大于90%。从这项研究中出现的原则可能会形成一个基础，解释的作用，个别基因的表达肿瘤的特点HUT-14细胞。
The modulation of gene expression accompanying neoplastic transformation has been assessed by computerized microdensitometry or autoradiographic patterns of [35S]methionine labeled polypeptides separated by two-dimensional polyacrylamide gel electrophoresis. Nearly 1000 polypeptide species of parent diploid human fibroblasts (KD strain) and clonally-derived malignant fibroblasts (HUT-14 strain) were compared. HUT-14 fibroblasts express a mutation in one of the two functional beta-actin genes and possess properties that distinguish them as neoplastic cells. Of the 700 more abundant polypeptides measured, 13 were lost and 14 were gained following this neoplastic transformation. It is estimated that less than or equal to 2% of the genes expressing abundant polypeptides were either activated or shut off, but at least 32% were modulated quantitatively as a consequence of this neoplastic transformation. Classes of "highly variable" and "marginally variable" polypeptides were assigned. Among the "highly variable" polypeptides, two related species barely detectable in KD parental cells were synthesized at a 25-31-fold higher rate in the transformed cells, and the cell-associated and extracellular matrix forms of fibronectin were each diminished by greater than 90%. Principles emerging from this study may form a basis for interpretation of the role of individual genes in the expression of neoplastic characteristics of HUT-14 cells.