Raloxifene plus 17beta-estradiol inhibits proliferation of primary cultured vascular smooth muscle cells and human mammary endothelial cells via the janus kinase/signal transducer and activator of transcription3 cascade
| Autor: | Qiu Ling Xiang, Hong Pan, Yu Hong Cui, Ting Huai Wang, Jian Wen Chen |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
STAT3 Transcription Factor
Selective Estrogen Receptor Modulators Vascular smooth muscle medicine.drug_class Blotting Western Estrogen receptor Fluorescent Antibody Technique Biology stat Muscle Smooth Vascular Rats Sprague-Dawley medicine Animals Estrogen Receptor beta Humans Raloxifene Breast Phosphorylation Cells Cultured Cell Proliferation Janus Kinases Pharmacology Estradiol Angiotensin II Endothelial Cells Tyrphostins Rats body regions Endothelial stem cell Selective estrogen receptor modulator Estrogen Raloxifene Hydrochloride Cancer research Drug Therapy Combination Female Janus kinase hormones hormone substitutes and hormone antagonists medicine.drug Signal Transduction |
| Zdroj: | European journal of pharmacology. 561(1-3) |
| ISSN: | 0014-2999 |
| Popis: | Long-term use of estrogen replacement therapy increases the risk of breast cancer. Presently, we investigated the effects and mechanisms of Raloxifene, a second generation selective estrogen receptor modulator, plus 17beta-estradiol on the proliferation of primary cultured vascular smooth muscle cells (VSMC) and human mammary endothelial cells (HMEC). Raloxifene plus 17beta-estradiol inhibited angiotensinII-induced VSMC proliferation and rapid phosphorylation of STAT 3 ; these effects were blocked by AG490, the janus kinase/signal transducer and activator of transcription3 (JAK/STAT 3 ) inhibitor. STAT 3 production was not affected. In primary cultured HMEC, immunofluorescence identified the ERbeta subtype, but not the ERalpha subtype, in the nucleus. Raloxifene plus 17beta-estradiol inhibited 17beta-estradiol-induced proliferation of HMEC. Western blot analysis established that Raloxifene attenuated the 17beta-estradiol-induced phosphorylation of STAT 3 , and that this effect was blocked by AG490. We conclude that Raloxifene plus 17beta-estradiol inhibits the proliferation of VSMC and HMEC through the JAK/STAT 3 cascade, which in primary cultured HMEC may be implemented through ERbeta. |
| Databáze: | OpenAIRE |
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