ArticleThe Journal of biological chemistry2013
STAT5 and prolactin participate in a positive autocrine feedback loop that promotes angiogenesis.
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.
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Who cites it
29 citing papers in PubMed, 63 citations in OpenAlex.
- Oncogenic driver and therapeutic target: Prolactin signalling axis in retroperitoneal sarcoma.Clinical and translational medicine · 2026Article
- The Interplay of Prolactin with Inflammatory Nutritional Markers and NT-proBNP in Chronic Kidney Disease.International journal of molecular sciences · 2025Observational
- 3D culturing as a promising strategy to enhance the angiogenic potential of adipose stem cell-derived secretome: insights into the role of miR-145-5p/ANGPT2 axis.Stem cell research & therapy · 2025Article
- Bidirectional crosstalk between sleep disorders and gynecological cancers: unraveling molecular synergies and precision therapeutics.Frontiers in medicine · 2025Review
- Single-cell insights: pioneering an integrated atlas of chromatin accessibility and transcriptomic landscapes in diabetic cardiomyopathy.Cardiovascular diabetology · 2024Article
- High STAT4 expression correlates with poor prognosis in acute myeloid leukemia and facilitates disease progression by upregulating VEGFA expression.Open medicine (Warsaw, Poland) · 2024Article
- Elevated levels of exogenous prolactin promote inflammation at the maternal-fetal interface via the JAK2/STAT5B signaling axis.Frontiers in immunology · 2024Article
- The role of prolactin/vasoinhibins in cardiovascular diseases.Animal models and experimental medicine · 2023Review
- MicroRNAs: A Link between Mammary Gland Development and Breast Cancer.International journal of molecular sciences · 2022Review
- Prolactin: The Third Hormone in Breast Cancer.Frontiers in endocrinology · 2022Review
- Meningeal CGRP-Prolactin Interaction Evokes Female-Specific Migraine Behavior.Annals of neurology · 2021Article
- The Relevant Participation of Prolactin in the Genesis and Progression of Gynecological Cancers.Frontiers in endocrinology · 2021Review
- Expression of IL-20 Receptor Subunit β Is Linked to EAE Neuropathology and CNS Neuroinflammation.Frontiers in cellular neuroscience · 2021Article
- Article
- 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 · 2019Review
- Suppressor of cytokine signalling-2 limits IGF1R-mediated regulation of epithelial-mesenchymal transition in lung adenocarcinoma.Cell death & disease · 2018Article
- Serelaxin treatment promotes adaptive hypertrophy but does not prevent heart failure in experimental peripartum cardiomyopathy.Cardiovascular research · 2017Article
- GDM alters paracrine regulation of feto-placental angiogenesis via the trophoblast.Laboratory investigation; a journal of technical methods and pathology · 2017Article
- Antagonizing STAT5B dimerization with an osmium complex.Scientific reports · 2016Article
- The role of the prolactin/vasoinhibin axis in rheumatoid arthritis: an integrative overview.Cellular and molecular life sciences : CMLS · 2016Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
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.
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Registered trials
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.