Kirjavainen J, Leppä S, Hynes N E, Jalkanen M
Department of Medical Biochemistry, University of Turku, Finland.
Mol Biol Cell. 1993 Aug;4(8):849-58. doi: 10.1091/mbc.4.8.849.
A cell surface proteoglycan, syndecan-1, has been shown to participate in the maintenance of the epithelial cell morphology. A point mutated activated c-Ha-ras gene under the control of the glucocorticoid inducible MMTV-LTR promoter was transfected into the mouse mammary epithelial cell line, NOG-8. The NOG-8 ras cells were used to study changes in syndecan-1 expression during epithelial transformation. NOG-8 ras cells, when induced to express Ha-ras, transformed and formed foci in monolayer cultures and colonies in suspension cultures. Expression of syndecan-1 at the cell surface was markedly reduced in cells showing the transformed phenotype. The accumulation of newly synthesized core protein of syndecan-1 was suppressed in these cells, whereas mRNA levels remained unchanged. This novel finding indicates that syndecan-1 expression is translationally suppressed in the Ha-ras-transformed epithelial cells. Hence, syndecan-1 loss during epithelial transformation could take place without altering syndecan gene transcription and, on the other hand, could be one of the critical events involved in malignant transformation.
细胞表面蛋白聚糖syndecan-1已被证明参与维持上皮细胞形态。将在糖皮质激素诱导型MMTV-LTR启动子控制下的点突变激活型c-Ha-ras基因转染到小鼠乳腺上皮细胞系NOG-8中。利用NOG-8 ras细胞研究上皮转化过程中syndecan-1表达的变化。当诱导表达Ha-ras时,NOG-8 ras细胞发生转化,在单层培养中形成集落,在悬浮培养中形成克隆。在表现出转化表型的细胞中,细胞表面syndecan-1的表达明显降低。这些细胞中syndecan-1新合成核心蛋白的积累受到抑制,而mRNA水平保持不变。这一新发现表明,在Ha-ras转化的上皮细胞中,syndecan-1的表达受到翻译抑制。因此,上皮转化过程中syndecan-1的缺失可能在不改变syndecan基因转录的情况下发生,另一方面,可能是恶性转化所涉及的关键事件之一。