We have updated our privacy policy. If you have any question, contact us at privacy@scicrunch.org. Dismiss and don't show again

Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Non-nuclear estrogen receptor alpha signaling promotes cardiovascular protection but not uterine or breast cancer growth in mice.

Steroid hormone receptors function classically in the nucleus as transcription factors. However, recent data indicate that there are also non-nuclear subpopulations of steroid hormone receptors, including estrogen receptors (ERs), that mediate membrane-initiated signaling of unclear basis and significance. Here we have shown that an estrogen-dendrimer conjugate (EDC) that is excluded from the nucleus stimulates endothelial cell proliferation and migration via ERalpha, direct ERalpha-Galphai interaction, and endothelial NOS (eNOS) activation. Analysis of mice carrying an estrogen response element luciferase reporter, ER-regulated genes in the mouse uterus, and eNOS enzyme activation further indicated that EDC specifically targets non-nuclear processes in vivo. In mice, estradiol and EDC equally stimulated carotid artery reendothelialization in an ERalpha- and G protein-dependent manner, and both agents attenuated the development of neointimal hyperplasia following endothelial injury. In contrast, endometrial carcinoma cell growth in vitro and uterine enlargement and MCF-7 cell breast cancer xenograft growth in vivo were stimulated by estradiol but not EDC. Thus, EDC is a non-nuclear selective ER modulator (SERM) in vivo, and in mice, non-nuclear ER signaling promotes cardiovascular protection. These processes potentially could be harnessed to provide vascular benefit without increasing the risk of uterine or breast cancer.

Pubmed ID: 20577047 RIS Download

Mesh terms: Animals | Antineoplastic Agents | Breast Neoplasms | Cell Line, Tumor | Cell Nucleus | Cell Proliferation | Endometrial Neoplasms | Enzyme Activation | Estradiol | Estrogen Receptor alpha | Estrogens | Female | Humans | Luciferases | Mice | Mice, Nude | Nitric Oxide Synthase Type III | Receptors, Estrogen | Response Elements | Signal Transduction | Uterus

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: CA18119
  • Agency: NIDDK NIH HHS, Id: DK15556
  • Agency: NIDDK NIH HHS, Id: R37 DK015556
  • Agency: NICHD NIH HHS, Id: HD30276
  • Agency: Intramural NIH HHS, Id: R01 DK056930
  • Agency: NIDDK NIH HHS, Id: R01 CA018119
  • Agency: NCI NIH HHS, Id: R01 DK015556
  • Agency: NIDDK NIH HHS, Id: DK56930
  • Agency: NIDDK NIH HHS, Id: R01 HD030276
  • Agency: NICHD NIH HHS, Id:

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.