Regulation of c-jun and jun-B by progestins in T-47D human breast cancer cells

Mol Endocrinol. 1992 Oct;6(10):1625-33. doi: 10.1210/mend.6.10.1448115.

Abstract

To investigate further the molecular mechanisms of progestin regulation of human breast cancer cell growth, we studied the effect of progestins on expression of the protooncogene c-jun and other members of the jun family, jun-B and jun-D, in T-47D human breast cancer cells. The progestin medroxyprogesterone acetate (MPA) increased c-jun mRNA levels in a time- and dose-dependent fashion. Maximal effects were seen after 3 h of treatment with 10-100 nM MPA. Under these conditions, the c-jun mRNA was increased 5.4-fold above the control level. Although the c-jun mRNA level was increased by cycloheximide alone, a further 2.4-fold increase was seen when the cells were treated with MPA in the presence of cycloheximide. The p39 c-jun protein was also increased 3.8-fold by this treatment. Maximum levels of p39 c-jun protein were achieved 9 h after treatment, and this level was maintained for at least 24 h. Dexamethasone and dihydrotestosterone did not increase the p39 c-jun protein level under these conditions. However, MPA treatment of T-47D cells resulted in a 55% decrease in overall AP-1 activity, as measured by transient transfection of an AP-1-regulated chloramphenicol acetyltransferase reporter gene. These effects were all reversible by cotreatment with a 10-fold higher concentration of the antiprogestin RU 486. MPA decreased jun-B mRNA levels 50% 1 h after treatment in T-47D cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Blotting, Western
  • Breast Neoplasms
  • Chloramphenicol O-Acetyltransferase / genetics
  • Chloramphenicol O-Acetyltransferase / metabolism
  • Cycloheximide / pharmacology
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Genes, jun* / drug effects
  • Humans
  • Kinetics
  • Medroxyprogesterone Acetate / pharmacology*
  • Multigene Family / drug effects
  • Proto-Oncogene Proteins c-jun / analysis
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins / metabolism
  • Transcription, Genetic / drug effects
  • Transfection
  • Tumor Cells, Cultured
  • beta-Galactosidase / genetics
  • beta-Galactosidase / metabolism

Substances

  • Proto-Oncogene Proteins c-jun
  • RNA, Messenger
  • Recombinant Proteins
  • Cycloheximide
  • Medroxyprogesterone Acetate
  • Chloramphenicol O-Acetyltransferase
  • beta-Galactosidase