Expression of prolactin mRNA and of prolactin-like proteins in endothelial cells: evidence for autocrine effects

Clapp, Carmen; López-Gómez, F J; Nava, Gabriel Miranda; Corbacho, Ana; Torner, Luz; Macotela, Yazmín; Dueñas, Zulma; Ochoa, Alejandra; Noris, Gino; Acosta, Elisa; Garay, Edith; Escalera, Gonzálo Martínez de la

doi:10.1677/joe.0.1580137

Cited by 65 publications

(58 citation statements)

References 34 publications

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“…U-PRL increased the expression of endogenous PRL by about 4-fold and doubled the expression of heme-oxygenase-1. Production of PRL by HUVEc has been previously reported (Clapp et al 1998, Corbacho et al 2000. In contrast to U-PRL, S179D PRL down-regulated the expression of endogenous PRL (about one-half) and heme-oxygenase-1 (about one-fourth), had no effect on the expression of what we labeled the long PRL receptor (which would include both the full-length and the deleted version) and up-regulated (doubled) both short forms of the PRLR.…”

Section: Effects On Gene Expression (Mrna)mentioning

confidence: 46%

A molecular mimic demonstrates that phosphorylated human prolactin is a potent anti-angiogenic hormone

Ueda

Özerdem

Chen

et al. 2006

Endocr Relat Cancer

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S179D prolactin (PRL) is an experimentally useful mimic of naturally phosphorylated human prolactin. S179D PRL, but not unmodified PRL, was found to be anti-angiogenic in both the chorioallantoic membrane and corneal assays. Further investigation using human endothelial in vitro models showed reduced cell number, reduced tubule formation in Matrigel, and reduced migration and invasion, as a function of treatment with S179D PRL. Analysis of growth factors in human endothelial cells in response to S179D PRL showed: a decreased expression or release of endogenous PRL, heme-oxygenase-1, basic fibroblast growth factor (bFGF), angiogenin, epidermal growth factor and vascular endothelial growth factor; and an increased expression of inhibitors of matrix metalloproteases. S179D PRL also blocked signaling from bFGF in these cells. We conclude that this molecular mimic of a pituitary hormone is a potent anti-angiogenic protein, partly as a result of its ability to reduce utilization of several well-established endothelial autocrine growth loops, partly by its ability to block signaling from bFGF and partly because of its ability to decrease endothelial migration. These findings suggest that circulating levels of phosphorylated PRL may influence the progression of cancer and, furthermore, that S179D PRL may be a useful anti-angiogenic therapeutic.

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Section: Effects On Gene Expression (Mrna)mentioning

confidence: 46%

A molecular mimic demonstrates that phosphorylated human prolactin is a potent anti-angiogenic hormone

Ueda

Özerdem

Chen

et al. 2006

Endocr Relat Cancer

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“…However, prolactin also acts as a cytokine and plays an important role in immune and inflammatory responses [49,50]. In addition, prolactin can act both as circulating hormone and as a paracrine/autocrine factor to either stimulate or inhibit various stages of the formation and remodeling of new blood vessels [51,52]. The formation of a new blood supply, angiogenesis, is an essential component of carcinogenesis and unrestricted tumor growth.…”

Section: Discussionmentioning

confidence: 99%

Development of multimarker panel for early detection of endometrial cancer. High diagnostic power of prolactin

Yurkovetsky

Ta’asan

Skates

et al. 2007

Gynecologic Oncology

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Objective-Endometrial carcinoma is the most common gynecologic cancer. Although the prognosis for endometrial cancer is generally good, cancers identified at late stages are associated with high levels of morbidity and mortality. Therefore, prevention and early detection may further reduce the burden of this challenging disease.Methods-A panel of 64 serum biomarkers was analyzed in sera of patients with stages I-III endometrial cancer and age-matched healthy women, utilizing a multiplex xMAP ™ bead-based immunoassay. For multivariate analysis, four different statistical classification methods were used: logistic regression (LR), separating hyperplane (SHP), k nearest neighbors (KNN), and Classification Tree (CART). For each of these classifiers a diagnostic model was created, based on the crossvalidation set consisting of sera from 115 patients with endometrial cancer and 135 healthy women.Results-Our data have demonstrated that patients with endometrial cancer have significantly different expression patterns of several serum biomarkers as compared to healthy controls. Prolactin was the strongest discriminative biomarker for endometrial cancer providing 98.3% sensitivity and 98.0% specificity alone. Our results have revealed that serum concentration of cancer antigens, including CA 125, CA 15-3, and CEA are higher in patients with Stage III endometrial cancer as compared to those with Stage I. In addition, we have shown that the expression of CA 125, AFP and ACTH is elevated in women with tumor grade 3 vs. grade 1. Furthermore, 5-biomarker panel Requests for reprints: Anna Lokshin, University of Pittsburgh Cancer Institute, Hillman Cancer Center, 5117 Centre Ave., Pittsburgh, PA 15213. Phone: 412-623-7706; Fax: 412-623-1415; E-mail: lokshina@pitt.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (prolactin, GH, Eotaxin, E-selectin, and TSH) identified in this study, was able to discriminate endometrial cancer from ovarian and breast cancers with high sensitivity and specificity. NIH Public AccessConclusions-The ability of prolactin to accurately discriminate between cancer and control groups indicates that this biomarker could potentially be used for development of blood-based test for the early detection of endometrial cancer in high-risk populations. Combining the information on multiple serum markers using flexible statistical methods allows for achieving high cancer selectivity.

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“…Total RNA from non-confluent HUVEC (1·5-2 10 6 cells/100 mm well) was isolated and RT-PCR performed essentially as described by Clapp et al (1998), using 40 cycles and an annealing temperature of 55 C. Two primers complementary to human PRL cDNA were synthesised: upstream primer from exon 2 (5 -GCAGTT GTTGTTGTGGATGATT-3 ) and downstream primer from exon 5 (5 -GATGCCAGGTGACCCTTCGAGA-3 ). RT-PCR products were identified by Southern blot using an homologous probe (human cDNA, American Type Culture Collection, Manassas, VA, USA) and a previously reported procedure .…”

Section: Reverse Transcriptase-polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

Human umbilical vein endothelial cells express multiple prolactin isoforms

Corbacho¹,

Macotela²,

Nava³

et al. 2000

Journal of Endocrinology

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Members of the prolactin (PRL) hormonal family have direct effects on endothelial cell proliferation, migration and tube formation. Moreover, isoforms of PRL may function as autocrine regulators of endothelial cells. Bovine brain capillary endothelial cells (BBCEC) express the PRL gene, while anti-PRL antibodies inhibit BBCEC proliferation. Here, we show the expression of the PRL gene into various PRL isoforms in endothelial cells from the human umbilical vein. Reverse transcription-polymerase chain reaction of total RNA from human umbilical vein endothelial cells (HUVEC) detected the full-length PRL mRNA as well as a 100 bp smaller PRL transcript similar to the one previously reported in BBCEC. HUVEC were positive to PRL immunocytochemistry. In addition, various PRL immunoreactive proteins were detected in HUVEC extracts and HUVEC conditioned media by metabolic labelling immunoprecipitation analysis. These PRL immunorelated proteins had apparent molecular masses of 60, 23, 21, 16 and 14 kDa. In contrast to previous findings in BBCEC, HUVEC conditioned media contained very little PRL bioactivity as determined by the selective bioassay of Nb2 cell proliferation. Moreover, some polyclonal or monoclonal antibodies directed against PRL stimulated HUVEC proliferation, in contrast to the inhibitory effect seen in BBCEC. The present findings extend the previous observations about the expression of PRL gene in endothelial cells from bovine brain capillaries to human cells of the umbilical vein, implicating that endothelium from different types of vessels and species share the expression of PRL gene but may differ in the putative autocrine role of the PRL isoforms expressed.

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Expression of prolactin mRNA and of prolactin-like proteins in endothelial cells: evidence for autocrine effects

Cited by 65 publications

References 34 publications

A molecular mimic demonstrates that phosphorylated human prolactin is a potent anti-angiogenic hormone

A molecular mimic demonstrates that phosphorylated human prolactin is a potent anti-angiogenic hormone

Development of multimarker panel for early detection of endometrial cancer. High diagnostic power of prolactin

Human umbilical vein endothelial cells express multiple prolactin isoforms

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