SV40 large-T oncogene inhibits transcription of perlecan-related proteoglycans but stimulates hyaluronan synthesis in a temperature-sensitive renal-tubule principal cell line

J Biol Chem. 1994 Jul 1;269(26):17469-76.

Abstract

We have analyzed the effects of SV40 large-T oncogene on proteoglycan (PG) synthesis in a temperature-sensitive SV40-transformed renal cell line. Cells shifted from permissive (33 degrees C) to restrictive (39.5 degrees C) temperature, acquired within 48 h the phenotype of principal cells of the renal collecting tubule. They then synthesized hyaluronan, a large-sized PG, small amounts of free GAG chains, and a major approximately 130-kDa heparan sulfate-PG. Sulfated PGs were localized in a basement membrane-like layer and possessed the same core protein (61-70 kDa) derived from perlecan. Expression of large-T oncogene at the permissive temperature induced dramatic alterations of the extracellular matrix, and a 4- and 12-fold reduction in cell-associated and medium-released sulfated PGs, due to a approximately 50% decrease in perlecan mRNA content and gene transcription. This contrasted with a 2-fold increase in actin gene transcription and a 10- and 2-fold rise in the hyaluronan content in cells and medium, respectively. These alterations did not occur in a control cell line (RC.SV3) derived from the same tubule segment but infected with wild-type SV40 strain. They are thus most likely related to the functional state of large-T oncogene and may take part in the early steps of transformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Polyomavirus Transforming / genetics*
  • Cell Line, Transformed
  • Chromatography, Ion Exchange
  • Glycosaminoglycans / metabolism
  • Heparan Sulfate Proteoglycans*
  • Heparitin Sulfate / genetics*
  • Heparitin Sulfate / metabolism
  • Hot Temperature
  • Hyaluronic Acid / biosynthesis*
  • Hyaluronic Acid / isolation & purification
  • Immunohistochemistry
  • Kidney Tubules, Collecting / cytology
  • Kidney Tubules, Collecting / metabolism*
  • Oncogenes*
  • Proteoglycans / genetics*
  • Proteoglycans / metabolism
  • Rabbits
  • Sulfuric Acids / metabolism
  • Transcription, Genetic*

Substances

  • Antigens, Polyomavirus Transforming
  • Glycosaminoglycans
  • Heparan Sulfate Proteoglycans
  • Proteoglycans
  • Sulfuric Acids
  • perlecan
  • Hyaluronic Acid
  • Heparitin Sulfate