Role of N-linked glycosylation in cell-cycle progression and initiation of DNA synthesis in tumor-transformed human fibroblasts

Anticancer Res. Jan-Feb 1993;13(1):167-71.

Abstract

In this study we show that proliferation of cycling tumor-transformed human fibroblasts (line 90VAV1) is blocked specifically in G1 by HMG CoA reductase inhibition. This inhibition also resulted in a drastic depression of N-linked glycosylation, measured as incorporation of radioactive glucosamine into acid-insoluble material. Following addition of mevalonate to cells arrested by HMG CoA reductase inhibitors, the depression of N-linked glycosylation was overcome and the cells initiated DNA synthesis. However, if the mevalonate-induced increase in protein glycosylation was prevented, due to addition of tunicamycin (an inhibitor of N-linked glycosylation), the cells were not able to proliferate. If instead tunicamycin was added 4 h after the addition of mevalonate, the cells synthesized DNA normally. Upon addition of tunicamycin, to cycling cells the progression through G1 was blocked in a similar way to that following HMG CoA reductase inhibition. Taken together, our data provide strong evidence for involvement of N-linked glycosylation in the mevalonate-controlled cell cycle progression and growth activation of tumor-transformed human fibroblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / drug effects
  • Cell Cycle / physiology
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cell Transformation, Neoplastic*
  • DNA, Neoplasm / biosynthesis*
  • Fibroblasts / metabolism
  • Fibroblasts / physiology*
  • Glycosylation
  • Humans
  • Hydroxycholesterols / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lovastatin / pharmacology
  • Neoplasm Proteins / metabolism
  • Stimulation, Chemical
  • Tunicamycin / physiology

Substances

  • DNA, Neoplasm
  • Hydroxycholesterols
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Neoplasm Proteins
  • Tunicamycin
  • 25-hydroxycholesterol
  • Lovastatin