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Fertil Steril. 2003 Feb;79(2):386-92.

Progestins activate vascular endothelial growth factor gene transcription in endometrial adenocarcinoma cells.

Author information

  • 1Department of Obstetrics and Gynecology, Inselspital, University of Bern, Bern, Switzerland. michel.mueller@insel.ch

Abstract

OBJECTIVE:

To determine whether progestins activate vascular endothelial growth factor (VEGF) gene transcription in endometrial adenocarcinoma cells.

DESIGN:

In vitro study.

SETTING:

University reproductive biology laboratories.

PATIENT(S):

None.

INTERVENTION(S):

Ishikawa cells were transfected with VEGF promoter-luciferase reporter constructs and expression vectors encoding human progesterone receptors (hPR) A or B. The cells were treated with different progestins and antiprogestins, and luciferase activity was compared with controls.

MAIN OUTCOME MEASURE(S):

Three functional progesterone response elements (PREs) in the VEGF promoter were identified by electrophoretic mobility-shift assay, and different constructs were created to assess each PRE.

RESULT(S):

In cells expressing hPRA or B, treatment with 10 nM R5020 or 100 nM medroxyprogesterone acetate statistically significantly increased luciferase activity (3.3- to 4.8-fold). Pretreatment with 100 nM RU486 blunted the effect of 10 nM R5020, resulting only in a slight, statistically nonsignificant increase in luciferase activity (1.3- to 1.7-fold). Although three different functional PREs could be identified, no single PRE accounted for the preponderance of the luciferase activity. Full VEGF promoter activation required all three PREs.

CONCLUSION(S):

Progestins have a direct effect on VEGF gene transcription. However, hPR-mediated transcriptional regulation of the VEGF promoter is complex and cannot be localized to confined PRE sequences. Other response element motifs are likely to play a contributory role.

PMID:
12568850
[PubMed - indexed for MEDLINE]
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