Induction of transforming growth factor alpha expression in mouse mammary epithelial cells after transformation with a point-mutated c-Ha-ras protooncogene

Mol Endocrinol. 1988 Dec;2(12):1202-16. doi: 10.1210/mend-2-12-1202.

Abstract

NOG-8 ras cells are a normal mouse mammary epithelial cell line transfected with a plasmid containing a glucocorticoid-inducible mouse mammary tumor virus long terminal repeat linked to the activated c-Ha-ras protooncogene. After addition of dexamethasone, there is a rapid induction (within 1-3 h) of p21ras protein that is concomitant with a parallel induction of the c-Ha-ras specific mRNA. After 4-6 days of dexamethasone treatment, NOG-8 ras cells are able to grow as colonies in semisolid medium. Between 9 and 12 days of dexamethasone treatment, there is a 5- to 6-fold increase of transforming growth factor alpha (TGF alpha) activity in the conditioned medium from NOG-8 ras cells. A 60-65% reduction in epidermal growth factor cell surface receptors on NOG-8 ras cells also occurs during this time interval. A 3- to 4-fold increase of the expression of a specific TGF alpha mRNA can be detected within 2 days of dexamethasone treatment, preceding the increase in TGF alpha protein found in the conditioned medium. Exogenous TGF alpha is able to stimulate in a dose-dependent fashion the anchorage-dependent and anchorage-independent growth of NOG-8 ras cells to a level comparable to that observed in dexamethasone treated ras-transformed NOG-8 ras cells. These results suggest that the enhanced expression of TGF alpha after induction of an activated ras protooncogene may be necessary for the anchorage-independent growth and subsequent morphological changes and the enhanced growth rate observed in ras-transformed mammary epithelial cells.

MeSH terms

  • Animals
  • Cell Line
  • Dexamethasone / pharmacology
  • Epithelial Cells
  • ErbB Receptors / genetics
  • Female
  • Gene Expression Regulation / drug effects*
  • Mammary Neoplasms, Experimental / metabolism
  • Mice
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / pharmacology*
  • Proto-Oncogene Proteins p21(ras)
  • Transformation, Genetic / drug effects*
  • Transforming Growth Factors / biosynthesis
  • Transforming Growth Factors / genetics*
  • Transforming Growth Factors / metabolism
  • Tumor Cells, Cultured

Substances

  • Proto-Oncogene Proteins
  • Transforming Growth Factors
  • Dexamethasone
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)