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

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.

• Authors: Michael D Mueller, Jean Louis Vigne, Elizabeth A Pritts, Victor Chao, Ekkehard Dreher, Robert N Taylor
• Journal: Fertility and sterility (Fertil Steril) Vol. 79 Issue 2 Pg. 386-92 (Feb 2003) ISSN: 0015-0282 [Print] United States
• PMID: 12568850 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Endothelial Growth Factors
• Intercellular Signaling Peptides and Proteins
• Lymphokines
• Receptors, Progesterone
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factors
• Mifepristone
• Promegestone
• Medroxyprogesterone

Topics

• Adenocarcinoma (genetics)
• Endometrial Neoplasms (genetics)
• Endothelial Growth Factors (genetics)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Intercellular Signaling Peptides and Proteins (genetics)
• Lymphokines (genetics)
• Medroxyprogesterone (pharmacology)
• Mifepristone (pharmacology)
• Promegestone (pharmacology)
• Receptors, Progesterone (physiology)
• Transcription, Genetic (drug effects)
• Transfection
• Tumor Cells, Cultured
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factors