Document Detail


Characterization of Δ7/11, a functional prolactin-binding protein.
MedLine Citation:
PMID:  23048206     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Prolactin is essential for normal mammary gland development and differentiation, and has been shown to promote tumor cell proliferation and chemotherapeutic resistance. Soluble isoforms of the prolactin receptor (PrlR) have been reported to regulate prolactin bioavailability by functioning as 'prolactin-binding proteins'. Included in this category is Δ7/11, a product of alternate splicing of the PrlR primary transcript. However, the direct interactions of prolactin with Δ7/11, and the resulting effect on cell behavior, have not been investigated. Herein, we demonstrate the ability of Δ7/11 to bind prolactin using a novel proximity ligation assay and traditional immunoprecipitation techniques. Biochemical analyses demonstrated that Δ7/11 was heavily glycosylated, similar to the extracellular domain of the primary PrlR, and that glycosylation regulated the cellular localization and secretion of Δ7/11. Low levels of Δ7/11 were detected in serum samples of healthy volunteers, but were undetectable in human milk samples. Expression of Δ7/11 was also detected in six of the 62 primary breast tumor biopsies analyzed; however, no correlation was found with Δ7/11 expression and tumor histotype or other patient demographics. Functional analysis demonstrated the ability of Δ7/11 to inhibit prolactin-induced cell proliferation as well as alter prolactin-induced rescue of cell cycle arrest/early senescence events in breast epithelial cells. Collectively, these data demonstrate that Δ7/11 is a novel regulatory mechanism of prolactin bioavailability and signaling.
Authors:
J M Fleming; E Ginsburg; C W McAndrew; C D Heger; L Cheston; J Rodriguez-Canales; B K Vonderhaar; P Goldsmith
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2012-12-31
Journal Detail:
Title:  Journal of molecular endocrinology     Volume:  50     ISSN:  1479-6813     ISO Abbreviation:  J. Mol. Endocrinol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-01     Completed Date:  2013-06-07     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  8902617     Medline TA:  J Mol Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  79-90     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Biopsy
Blotting, Western
Breast Neoplasms / metabolism,  pathology
CHO Cells
Carrier Proteins / blood,  metabolism*
Cell Cycle
Cell Line, Tumor
Cell Proliferation
Cricetinae
Cricetulus
Female
Glycosylation
Humans
Immunoprecipitation
Milk, Human / metabolism
Polymerase Chain Reaction
Prolactin / metabolism
Protein Binding
Recombinant Proteins / blood,  metabolism
Grant Support
ID/Acronym/Agency:
U54 CA156735/CA/NCI NIH HHS; U54 CA156735/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Recombinant Proteins; 0/prolactin-binding protein; 9002-62-4/Prolactin
Comments/Corrections

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