JAK2/STAT5 Pathway Mediates Prolactin-Induced Apoptosis of Lactotropes

Dios, Nataly de; Orrillo, Santiago Jordi; Irizarri, Martín; Theas, María Susana; Boutillon, Florence; Candolfi, Marianela; Seilicovich, Adriana; Goffin, Vincent; Pisera, Daniel; Ferraris, Jimena

doi:10.1159/000494975

Cited by 18 publications

(10 citation statements)

References 53 publications

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“…Cells were seeded in 24-well plates and cultured in 200 μl/well for 48 h. Then, supernatants were collected and cell proteins were extracted as described above. PRL levels were measured by RIA using reagents provided by the National Institute of Diabetes and Digestive and Kidney Diseases, National Hormone and Pituitary Program (Torrance, CA) as previously described 69 .…”

Section: Methodsmentioning

confidence: 99%

Prolactin and its receptor as therapeutic targets in glioblastoma multiforme

Asad

Candia

González

et al. 2019

Sci Rep

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Although prolactin (PRL) and its receptor (PRLR) have been detected in glioblastoma multiforme (GBM), their role in its pathogenesis remains unclear. Our aim was to explore their contribution in GBM pathogenesis. We detected PRL and PRLR in all GBM cell lines tested. PRLR activation or overexpression using plasmid transfection increased proliferation, viability, clonogenicity, chemoresistance and matrix metalloproteinase activity in GBM cells, while PRLR antagonist ∆1–9-G129R-hPRL reduced their proliferation, viability, chemoresistance and migration. Meta-analysis of transcriptomic data indicated that PRLR was expressed in all grade II-III glioma (GII-III) and GBM samples. PRL was upregulated in GBM biopsies when compared to GII-III. While in the general population tumour PRL/PRLR expression did not correlate with patient survival, biological sex-stratified analyses revealed that male patients with PRL+/PRLRHIGH GBM performed worse than PRL+/PRLRLOW GBM. In contrast, all male PRL+/PRLRHIGH GII-III patients were alive whereas only 30% of PRL+/PRLRLOW GII-III patients survived after 100 months. Our study suggests that PRLR may be involved in GBM pathogenesis and could constitute a therapeutic target for its treatment. Our findings also support the notion that sexual dimorphism should be taken into account to improve the care of GBM patients.

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Section: Methodsmentioning

confidence: 99%

Prolactin and its receptor as therapeutic targets in glioblastoma multiforme

Asad

Candia

González

et al. 2019

Sci Rep

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“…proven by many studies. Prolactin as a polypeptide hormone is secreted primarily by lactotroph cells of the pituitary gland(de Dios et al, 2019). Prolactin either indirectly regulates testicular function by regulating the release of gonadotropins from the pituitary gland, or by directly increasing the amount of LH receptors on Leydig cells in the testis.…”

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confidence: 99%

Protective effect of Feijoa sellowianan fruit on testicular toxicity‐induced by cadmium chloride

et al. 2020

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Cadmium chloride (CdCl 2) as an environmental and industrial toxin has a significant detrimental effect on the testis (Nna et al., 2017). CdCl 2 is in the heavy metal group that is primarily released from colour pigments, TV screens, plating, battery manufacturing, plastics and fertilisers, and mining activities (Saini & Dhania, 2020). This combination enters the human body through contaminated food, drinking water and inhalation of air containing CdCl 2 particles or smoke containing CdCl 2 due to occupational exposure or air pollution caused by jungle fire (Rehman et al., 2018). Also, nutrition is the main source of absorption of CdCl 2. Vegetables and grains that grow in CdCl 2-contaminated soils or soils that are naturally high in CdCl 2 to be the main source of nonworking conditions exposure (Chunhabundit, 2016). Tobacco plants selectively absorb CdCl 2 from the soil and tobacco consumption increases the level of CdCl 2 in the human body. CdCl 2 can enter the lungs through tobacco smoke (Ganguly et al., 2018) and then circulate CdCl 2 throughout the body. In the liver, CdCl 2 with proteins forms a complex that is eventually secreted by the kidneys (Shirriff & Heikkila, 2017). CdCl 2 concentration in the blood of smokers is 4-5 times and in kidney 2-3 times higher than nonsmokers (Mannino et al., 2004; Mazur et al., 2018). The half-life of cadmium in the blood is estimated at 75-128 days, which means that CdCl 2 is deposited in organs including the liver, kidney and reproductive system and is not excreted from the body (Thompson & Bannigan, 2008). CdCl 2 causes hepatotoxicity (Almeer et al., 2018), nephrotoxicity (Sadek et al., 2017) hematotoxicity (Pagano et al., 2017), cardiotoxicity (Shrivastava et al., 2019) and skeletal muscle injury (Al-Sawafi et al., 2017). Epidemiological studies have shown that CdCl 2 has negative effects on sex hormone concentrations, sperm parameters and male infertility (Olaniyan et al., 2018). Cd with rupture

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“…Key proteins in the cAMP, PI3K-Akt, Prolactin, and Ras pathways and PPI networks obtained from KEGG pathway enrichment analysis interact with each other to form a complex target−pathway network. For example, the downstream proteins of the Prolactin pathway are JAK2, MAPK, and SRC and regulate apoptosis and inflammation through the JAK/STAT pathway [61][62][63]. MAPK integrates crosstalk with multiple signaling pathways, such as the Ras/MAPK pathway, ErbB pathway, and PI3K-Akt pathway.…”

Section: Discussionmentioning

confidence: 99%

Integrating Network Pharmacology and Molecular Docking to Analyse the Potential Mechanism of action of Macleaya cordata (Willd.) R. Br. in the Treatment of Bovine Hoof Disease

Dong

Liu

Zou

et al. 2021

Veterinary Sciences

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Based on network pharmacological analysis and molecular docking techniques, the main components of M. cordata for the treatment of bovine relevant active compounds in M. cordata were searched for through previous research bases and literature databases, and then screened to identify candidate compounds based on physicochemical properties, pharmacokinetic parameters, bioavailability, and drug-like criteria. Target genes associated with hoof disease were obtained from the GeneCards database. Compound−target, compound−target−pathway−disease visualization networks, and protein−protein interaction (PPI) networks were constructed by Cytoscape. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed in R language. Molecular docking analysis was done using AutoDockTools. The visual network analysis showed that four active compounds, sanguinarine, chelerythrine, allocryptopine and protopine, were associated with the 10 target genes/proteins (SRC, MAPK3, MTOR, ESR1, PIK3CA, BCL2L1, JAK2, GSK3B, MAPK1, and AR) obtained from the screen. The enrichment analysis indicated that the cAMP, PI3K-Akt, and ErbB signaling pathways may be key signaling pathways in network pharmacology. The molecular docking results showed that sanguinarine, chelerythrine, allocryptopine, and protopine bound well to MAPK3 and JAK2. A comprehensive bioinformatics-based network topology strategy and molecular docking study has elucidated the multi-component synergistic mechanism of action of M. cordata in the treatment of bovine hoof disease, offering the possibility of developing M. cordata as a new source of drugs for hoof disease treatment.

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JAK2/STAT5 Pathway Mediates Prolactin-Induced Apoptosis of Lactotropes

Cited by 18 publications

References 53 publications

Prolactin and its receptor as therapeutic targets in glioblastoma multiforme

Prolactin and its receptor as therapeutic targets in glioblastoma multiforme

Protective effect of Feijoa sellowianan fruit on testicular toxicity‐induced by cadmium chloride

Integrating Network Pharmacology and Molecular Docking to Analyse the Potential Mechanism of action of Macleaya cordata (Willd.) R. Br. in the Treatment of Bovine Hoof Disease

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