Regulation of transforming growth factor gene expression in human endometrial adenocarcinoma cells.

Abstract

We have examined the effects of medroxyprogesterone acetate (MPA) and 4-hydroxytamoxifen (OH-TAM) on the cell proliferation and the expression of TGF-alpha and TGF-beta genes in Ishikawa cells and HEC-50 human endometrial adenocarcinoma cells. The effects of exogenous TGF-alpha, TGF-beta and anti-EGF receptor monoclonal antibody on cell proliferation were also determined. Antisense oligonucleotides were used to determine the effects of endogenous expression of TGF-alpha and TGF-beta. In both cell lines, MPA resulted in a time and dose-dependent inhibition of cell proliferation whereas OH-TAM had no effect on HEC-50 cell proliferation. The relative abundance of TGF-alpha mRNA was significantly reduced by MPA in Ishikawa cells but not in HEC-50 cells. In Ishikawa cells, a reduction in TGF-alpha mRNA abundance was observed with OH-TAM under conditions where both inhibition and stimulation of cell proliferation were demonstrated. Anti-EGF receptor monoclonal antibody inhibited Ishikawa cell growth but had little effect on HEC-50 cell proliferation. Exogenous TGF-alpha stimulated proliferation of both cell lines whereas exogenous TGF-beta inhibited proliferation of Ishikawa cells but stimulated proliferation of HEC-50 cells. Antisense oligonucleotides to TGF-beta inhibited proliferation of HEC-50 cells. From these data we conclude that the antiproliferative effects of progestins and OH-TAM on endometrial cancer cells appear to be mediated by different mechanisms.

• Authors: L J Murphy, Y Gong, L C Murphy
• Journal: The Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 41 Issue 3-8 Pg. 309-14 (Mar 1992) ISSN: 0960-0760 [Print] England
• PMID: 1532902 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Estrogen Antagonists
• Oligonucleotides, Antisense
• Steroids
• Transforming Growth Factor alpha
• Transforming Growth Factor beta
• Tamoxifen
• afimoxifene
• Medroxyprogesterone Acetate
• Medroxyprogesterone

Topics

• Adenocarcinoma (genetics)
• Antineoplastic Agents (pharmacology)
• Cell Division (drug effects)
• Cell Line
• Endometrial Neoplasms (genetics)
• Estrogen Antagonists (pharmacology)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Medroxyprogesterone (analogs & derivatives, pharmacology)
• Medroxyprogesterone Acetate
• Oligonucleotides, Antisense (pharmacology)
• Steroids (pharmacology)
• Tamoxifen (analogs & derivatives, pharmacology)
• Transforming Growth Factor alpha (genetics, pharmacology)
• Transforming Growth Factor beta (genetics, pharmacology)