Evidence map›Paper›PMID 23729680›Full record

ArticleThe Journal of biological chemistry2013

STAT5 and prolactin participate in a positive autocrine feedback loop that promotes angiogenesis.

Xinhai Yang, Kristy Meyer, Andreas Friedl

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
3.0field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 63 citations in OpenAlex.

  1. Article
  2. Observational
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. The role of prolactin/vasoinhibins in cardiovascular diseases.Animal models and experimental medicine · 2023
    Review
  9. MicroRNAs: A Link between Mammary Gland Development and Breast Cancer.International journal of molecular sciences · 2022
    Review
  10. Prolactin: The Third Hormone in Breast Cancer.Frontiers in endocrinology · 2022
    Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Role of pregnancy hormones and hormonal interaction on the maternal cardiovascular system: a literature review.Clinical research in cardiology : official journal of the German Cardiac Society · 2019
    Review
  16. Article
  17. Article
  18. GDM alters paracrine regulation of feto-placental angiogenesis via the trophoblast.Laboratory investigation; a journal of technical methods and pathology · 2017
    Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Xinhai YangFrom the Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin 53705.
Kristy MeyerFrom the Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin 53705.
Andreas FriedlFrom the Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin 53705,; Pathology and Laboratory Medicine Service, William S. Middleton Memorial Veterans Hospital, Department of Veterans Affairs Medical Center, Madison, Wisconsin 53705, and; UW Carbone Cancer Center, Madison, Wisconsin 53792. Electronic address: afriedl@wisc.edu.
University of Wisconsin–Madison · US

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI AMY TRENTHAM-DIETZ · 1985 to 2026
$142.6M
STATs as Key Targets in Tumor AngiogenesisI01BX000137 · VA · WM S. MIDDLETON MEMORIAL VETERANS HOSP · PI FRIEDL, ANDREAS · 2009 to 2016
–
BLRD VA I01 BX000137NCI NIH HHS P30 CA014520
6 · The paper itself

Abstract

We have shown previously that the murine prolactin/growth hormone family member proliferin plays a pivotal role in angiogenesis induced by the FGF2/STAT5 signaling cascade. To delineate the signaling pathway downstream of STAT5 in the human system, where proliferin does not exist, we expressed constitutively active (CA) or dominant-negative (DN) mutant STAT5A in hCMEC/D3 human brain endothelial cells. We found that conditioned medium from CA-STAT5A- but not from DN-STAT5A-overexpressing endothelial cells (EC) is sufficient to induce EC migration and tube formation but not proliferation, indicating that STAT5A regulates the secretion of autocrine proangiogenic factors. We identified prolactin (PRL) as a candidate autocrine factor. CA-STAT5A expression stimulates PRL production at the RNA and protein level, and STAT5A binds to the PRL promoter region, suggesting direct transcriptional regulation. Medium conditioned by CA-STAT5A-overexpressing EC induces phosphorylation of the PRL receptor and activates MAPK. Knockdown of PRL expression by shRNA or blocking of PRL activity with neutralizing antibodies removed the CA-STAT5A-dependent proangiogenic activity from the conditioned medium of EC. The addition of recombinant PRL restores this activity. STAT5A-induced PRL in the conditioned medium can activate STAT5, STAT1, and to a lesser extent STAT3 in hCMEC/D3 cells, suggesting the existence of a positive feedback loop between STAT5 and PRL that promotes angiogenesis. Furthermore, we find that VEGF, a potent proangiogenic factor, is induced by activation of STAT5A, and VEGF induction depends on PRL expression. These observations demonstrate a STAT5/PRL/VEGF signaling cascade in human brain EC and implicate PRL and VEGF as autocrine regulators of EC migration, invasion, and tube formation.

Indexed as

Autocrine CommunicationFeedback, PhysiologicalNeovascularization, PhysiologicAngiogenesis Inducing AgentsAnimalsCell MovementCell ProliferationCulture Media, ConditionedEndothelial CellsExtracellular Signal-Regulated MAP KinasesGene SilencingHumansMicePhosphorylationProlactinPromoter Regions, GeneticAngiogenesis Inducing AgentsCulture Media, ConditionedExtracellular Signal-Regulated MAP KinasesProlactinReceptors, ProlactinRNA, Small InterferingSTAT5A protein, humanSTAT5 Transcription FactorTumor Suppressor ProteinsVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2AngiogenesisAutocrine FactorsCell MigrationCell SignalingProlactinSTAT5STAT Transcription Factor

Identifiers

PMID23729680
PMCPMC3774384
OpenAlexW2016852812

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.