Expression of cartilage extracellular matrix and potential regulatory genes in a new human chondrosarcoma cell line
Expression of cartilage extracellular matrix and potential regulatory genes in a new human chondrosarcoma cell line
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DOI：
10.1002/jor.1100160502
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发表时间：
1998-09-01
影响因子：
2.8
通讯作者：
Sandell, LJ
中科院分区：
文献类型：
--
作者：
Chansky, H;Robbins, JR;Sandell, LJ
一个人软骨肉瘤细胞系已经建立了一个积极的软骨肉瘤。细胞在单层培养物中生长（倍增时间：2天）并形成聚集体。聚集体由围绕中空核的细胞边缘组成。该细胞系表现出独特的mRNA表达模式，具有软骨细胞表型的几种分子特征。与软骨细胞表型一致，存在编码IX和XI型胶原的mRNA，同时沿着编码软骨蛋白聚糖双糖蛋白聚糖和聚集蛋白聚糖的核心蛋白的mRNA的丰富表达。未观察到编码I型或II型纤维状胶原或蛋白多糖核心蛋白聚糖的mRNA的表达。[S-35]硫酸盐放射性标记材料的十二烷基硫酸钠-聚丙烯酰胺凝胶电泳分析证实了含有糖胺聚糖链的蛋白聚糖的翻译。检测了有助于软骨发育和肿瘤发生的分子的表达。该细胞系产生丰富的mRNA，编码转化生长因子β 1，软骨和骨诱导蛋白家族的成员。检测到编码两种与软骨发生特异性相关的蛋白质的mRNA的表达：Cart-1，一种参与软骨分化的同源框蛋白，和CD-RAP，一种在正常条件下限制分化软骨细胞和软骨的分泌分子。检测到抑癌基因p53的过表达。DNA分析显示编码p53的染色体位点的杂合性丢失，在亲本肿瘤和细胞系中一个p53等位基因缺失，其余等位基因突变。恶性软骨肉瘤表型可能与独特的基因表达模式有关，该基因表达模式在许多分化成软骨细胞的方式中是特征性的，以及与可能有助于细胞系增殖能力的p53功能失活有关。该细胞系可作为进一步研究人类软骨肉瘤病因学和软骨特异性基因合成与调控的生物学模型。
A human chondrosarcoma cell line has been established from an aggressive chondrosarcoma. The cells grow in a monolayer culture (doubling time: 2 days) and form aggregates. The aggregates consist of a rim of cells surrounding a hollow core. The cell line exhibits a unique pattern of mRNA expression with several molecules characteristic of the chondrocyte phenotype. Consistent with the chondrocyte phenotype, mRNAs encoding types IX and XI collagens were present along with an abundant expression of mRNAs encoding the core protein of the cartilage proteoglycans biglycan and aggrecan. No expression of mRNAs encoding types I or II fibrillar collagens or the proteoglycan decorin was observed. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of [S-35]sulfate-radiolabeled material confirmed the translation of proteoglycans containing glycosaminoglycan chains. The expression of molecules that contribute to cartilage development and tumorigenesis was examined. The cell line produces abundant mRNA that encodes transforming growth factor-beta 1, a member of a family of cartilage and bone inductive proteins. The expression of mRNA encoding two proteins associated specifically with chondrogenesis was detected: Cart-1, a homeobox protein involved in cartilage differentiation, and CD-RAP, a secreted molecule restricted under normal conditions to differentiating chondrocytes and cartilage. Overexpression of p53, a tumor-suppressor gene, was detected. DNA analysis revealed a loss of heterozygosity at the chromosomal locus encoding p53, with the deletion of one p53 allele and the mutation of the remaining allele in both the parent tumor and the cell line. The malignant chondrosarcoma phenotype may be related to the unique gene expression pattern that is characteristic in many ways of differentiating chondroblasts, as well as to the inactivation of the p53 function that could contribute to the proliferative capacity of the cell Line. This cell line may serve as a biological model for further investigation of the etiology of human chondrosarcomas and for the synthesis and regulation of cartilage-specific genes.