IndraLab
Statements
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"Short term incubation (< 60 min) of prolactin responsive Nb2 lymphoma cells at high density selectively blocked prolactin stimulation of p42 and p44 mitogen activated protein kinases and transcription factors Stat1 and Stat3 but not prolactin activation of Stat5 or the tyrosine kinase Jak2."
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"XREF_BIBR, XREF_BIBR Restoring PRL receptor expression in TNBC cell lines decreases their invasive capacity while blocking JAK2 and STAT5 in luminal breast cancer cell lines increases their invasiveness, suggesting that PRL activation of STAT5 restricts the metastatic potential of breast tumors."
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"Not only has this work elegantly and conclusively shown that the PI3K and Akt pathway induces autocrine prolactin production which is required for the initiation of lactation, but it has the additional merit of the use of genetically altered mouse models to study the activation of STAT5 by prolactin in vivo in the correct cellular environment so we can be confident that the data are biologically relevant."
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"In a separate assay to quantify the percentage of cells in which Prl induced Stat5 translocation to the nucleus, monolayer cultured cells were differentiated by adding diluted BM matrix to the culture medium (i.e., 2D culture with BM overlay) before stimulation with Prl for 15 min."
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"In epidemiologic studies, the presence of prolactin and phosphorylated signal transducer and activator of transcription 5 (STAT5) in human prostate cancers is linked with high-grade tumors and more aggressive disease [XREF_BIBR]; therefore, targeting autocrine and/or paracrine prolactin mediated activation of STAT5 may represent a novel therapeutic target for patients with prostate cancer."
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"In mammary glands, PRL activated Stat5 in a majority of luminal epithelial cells but not myoepithelial cells, stromal fibroblasts, or adipocytes, whereas GH activated Stat5 in a significant fraction of myoepithelial cells, fibroblasts, and adipocytes but only in a minority of luminal cells."
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"In addition to its pivotal role for mammary epithelial cell proliferation, specification, and differentiation, we demonstrate that this kinase is indispensable for the prolactin mediated activation of Stat5 and the maintenance of functionally differentiated alveolar cells during lactation."
| PMC
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"Although PRL is a known activator of STAT5 in the mammary gland, these data showing ErbB3 dependent induction of STAT5 expression, taken with previous data demonstrating ErbB4 mediated phosphorylation and activation of STAT5, suggest that NRGs produced locally in the mammary microenvironment enable PRL mediated STAT5A activation, while at the same time promoting PI3K and Akt signaling, which together amplify, sustain, and differentiate this unique cell population on which newborn mammals depend."
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"Our data indicate that in the mammary gland CIS and SOCS3 are involved in regulating STAT5 signaling at three different instances : 1) SOCS3 serves as a mediator of the inhibitory EGF effect on PRL induced STAT5 activation; 2) CIS and SOCS3 play a role as negative feedback inhibitors of PRL action; 3) Inhibition of CIS and SOCS3 expression by glucocorticoids contributes to the positive effect of glucocorticoids on PRL induced STAT5 activation."
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"In recent studies, we have demonstrated in breast cancer ERalpha + and HER2 + cells, up-regulation of PRLR transcription and expression induced by endogenous and exogenous PRL in the absence of estrogen via the long form of the prolactin receptor with essential participation of ERalpha and JAK2 and STAT5, mitogen activated protein kinase (MAPK) and PI3K pathways [XREF_BIBR]."
sparser
"Second, β1 integrins are actively required for Prl signaling both in culture and in vivo because function-perturbing anti–β1 integrin antibodies block MEC differentiation ( xref ), a dominant-negative (DN) β1 integrin transgene compromises Stat5 activation and milk production ( xref ), and Prl cannot activate Stat5 in β1 integrin–null MECs ( xref )."
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"Second, beta1 integrins are actively required for Prl signaling both in culture and in vivo because function perturbing anti-beta1 integrin antibodies block MEC differentiation, a dominant negative (DN) beta1 integrin transgene compromises Stat5 activation and milk production, and Prl can not activate Stat5 in beta1 integrin-null MECs."
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"Examining six different cancer cell lines with wild type BRCA1, and making use of both prolactin and the growth inhibiting selective prolactin receptor modulator, S179D PRL, we demonstrate that prolactin activation of Stat5 results in the formation of a complex between phospho-Stat5 and BRCA1."
sparser
"STAT5 pathway activation by PRL in these experiments is evident in regulation of multiple STAT5 target genes, including the immune system modulating genes and pathways: IL-2, IL-3 and Bcl-2 signaling, Il2ra , Tnfsf10 , Foxp3, Slfn2, C3ar1, Osm, Socs1 , etc. ( xref ; xref ; xref ) (Supplementary Excel files/material)."
sparser
"Examining six different cancer cell lines with wild type BRCA1, and making use of both prolactin and the growth-inhibiting selective prolactin receptor modulator, S179D PRL, we demonstrate that prolactin activation of Stat5 results in the formation of a complex between phospho-Stat5 and BRCA1."
sparser
"In mammary glands, PRL activated Stat5 in a majority of luminal epithelial cells but not myoepithelial cells, stromal fibroblasts, or adipocytes, whereas GH activated Stat5 in a significant fraction of myoepithelial cells, fibroblasts, and adipocytes but only in a minority of luminal cells."
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"To understand the intrinsic effect of 17beta-estradiol (E2) and ICI on expression of the STAT5 isoforms and how these outcomes affect the interplay with PRL activated STAT5 isoforms in mammary epithelia of differing phenotypes, we compared the well characterized, differentiated HC11 mouse cell line [XREF_BIBR] and ERalpha + mouse mammary tumor cell (TC) lines generated from PRL induced adenocarcinomas [XREF_BIBR]."
sparser
"Not only has this work elegantly and conclusively shown that the PI3K/Akt pathway induces autocrine prolactin production which is required for the initiation of lactation, but it has the additional merit of the use of genetically altered mouse models to study the activation of STAT5 by prolactin in vivo in the correct cellular environment so we can be confident that the data are biologically relevant."
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"Given the important role for estrogens in maternal behavior and the recent finding that PRL treatment enhances STAT5 activity in ERalpha neurons in the female mouse brain, the relationships between alterations in neural sensitivity to PRL and the apparent shift in estrogen receptor activity may play an important role in regulating enhancements of maternal care, i.e. the retention of maternal behavior, long after the cessation of lactation."
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"Stat5 chromatin immunoprecipitation demonstrated physical interaction with a BCL6 gene regulatory region, and BCL6 transcript repression required histone deacetylase activity based on sensitivity to trichostatin A. Functionally, BCL6 overexpression disrupted prolactin induction of Stat5 reporter genes."
sparser
"Our data indicate that in the mammary gland CIS and SOCS3 are involved in regulating STAT5 signaling at three different instances: 1) SOCS3 serves as a mediator of the inhibitory EGF effect on PRL-induced STAT5 activation; 2) CIS and SOCS3 play a role as negative feedback inhibitors of PRL action; 3) Inhibition of CIS and SOCS3 expression by glucocorticoids contributes to the positive effect of glucocorticoids on PRL-induced STAT5 activation."
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"The present study of prolactin (PRL) receptor mediated recruitment of signal transducers and activators of transcription (STATs) demonstrates that PRL activates STAT3, in addition to STAT1 and STAT5 as previously reported, and that STAT1, STAT3 and STAT5 are mediators of PRL effects in cells whether of lymphoid, myeloid or mammary epithelial origin."
sparser
"Short term incubation (<60 min) of prolactin-responsive Nb2 lymphoma cells at high density selectively blocked prolactin stimulation of p42/p44 mitogen-activated protein kinases and transcription factors Stat1 and Stat3 but not prolactin activation of Stat5 or the tyrosine kinase Jak2."
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"It remains to be seen whether the increased beta-cell replication observed in pregnancy is also achieved through this mechanism, but evidence suggests that in pregnancy, prolactin not only increases STAT5 signalling, it also reduces the levels of the tumour suppressor gene menin, which is a known inhibitor of Cdk2 activity [XREF_BIBR]."
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"PRL stimulates the Jak and Stat pathway (Jak2 and Stat5) in the mammary gland, which is responsible for the induction of milk protein expression in BMEC as well as other mammary epithelial cells due to the presence of Stat5 binding sites on the epithelial cells, and this could be a potential regulatory pathway by which 5-HT acts through 5-HT 2A."
sparser
"Although the PRL-induced activation of Jak2 and Stat5 is able to regulate the levels of active Akt1 and nuclear accumulation of Cyclin D1 in normal cells ( xref ; xref ; xref ), we have demonstrated recently that the expression of constitutively active ErbB2 was sufficient to elevate the expression of these downstream mediators independently of Jak2."
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"It remains to be seen whether the increased beta-cell replication observed in pregnancy is also achieved through this mechanism, but evidence suggests that in pregnancy, prolactin not only increases STAT5 signalling, it also reduces the levels of the tumour suppressor gene menin, which is a known inhibitor of Cdk2 activity [XREF_BIBR, XREF_BIBR]."
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"We report that (i) Stat5 is the major signaling cascade triggered by local PRL in the mouse dorsal prostate, (ii) this model recapitulates prostate tumorogenesis from precancer lesions to invasive carcinoma, and (iii) tumorogenesis involves dramatic accumulation and abnormal spreading of p63 positive basal cells, and of stem cell antigen-1-positive cells identified as a stem and progenitor like subpopulation."