TRANSLATIONAL SUPPRESSION OF SYNDECAN-1 EXPRESSION IN HA-RAS TRANSFORMED MOUSE MAMMARY EPITHELIAL-CELLS

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.