Overexpression of parathyroid hormone-related protein or parathyroid hormone in transgenic mice impairs branching morphogenesis during mammary gland development

Parathyroid hormone-related protein (PTHrP) was originally discovered as the tumor product that causes humoral hypercalcemia of malignancy. PTHrP is now known to be widely expressed in many normal fetal tissues where it may participate in the regulation of organogenesis. In this report, we document...

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Veröffentlicht in:Development (Cambridge) 1995-11, Vol.121 (11), p.3539-3547
Hauptverfasser: Wysolmerski, J J, McCaughern-Carucci, J F, Daifotis, A G, Broadus, A E, Philbrick, W M
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container_end_page 3547
container_issue 11
container_start_page 3539
container_title Development (Cambridge)
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creator Wysolmerski, J J
McCaughern-Carucci, J F
Daifotis, A G
Broadus, A E
Philbrick, W M
description Parathyroid hormone-related protein (PTHrP) was originally discovered as the tumor product that causes humoral hypercalcemia of malignancy. PTHrP is now known to be widely expressed in many normal fetal tissues where it may participate in the regulation of organogenesis. In this report, we document that overexpression of PTHrP in myoepithelial cells in the mammary glands of transgenic mice resulted in a form of breast hypoplasia characterized by a profound defect in branching morphogenesis of the developing mammary duct system. In addition, transgenic mice manifested a defect in lobuloalveolar development during pregnancy that seemed to be, in part, the consequence of an impaired ability to form terminal ducts in response to estrogen and progesterone stimulation. The effects of PTHrP on branching morphogenesis during breast development appeared to be the result of amino-terminal PTH-like sequences that signal through the PTH/PTHrP receptor, since overexpression of parathyroid hormone itself in the mammary glands of transgenic mice caused a similar development phenotype, and delivery of PTHrP (1–36) via locally implanted slow-release pellets impaired breast development in normal mice. These results suggest that PTHrP, which is a native product of mammary epithelial and myoepithelial cells may participate in normal breast development, perhaps as a locally secreted growth inhibitor.
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The effects of PTHrP on branching morphogenesis during breast development appeared to be the result of amino-terminal PTH-like sequences that signal through the PTH/PTHrP receptor, since overexpression of parathyroid hormone itself in the mammary glands of transgenic mice caused a similar development phenotype, and delivery of PTHrP (1–36) via locally implanted slow-release pellets impaired breast development in normal mice. 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identifier ISSN: 0950-1991
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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; Company of Biologists
subjects Animals
Base Sequence
Cell Culture Techniques
Drug Implants
Epithelium - embryology
Female
Gene Expression
Immunohistochemistry
Mammary Glands, Animal - cytology
Mammary Glands, Animal - drug effects
Mammary Glands, Animal - embryology
Mesoderm - physiology
Mice
Mice, Transgenic
Molecular Sequence Data
Morphogenesis - genetics
Parathyroid Hormone - genetics
Parathyroid Hormone - metabolism
Parathyroid Hormone-Related Protein
Polymerase Chain Reaction
Proteins - genetics
Proteins - metabolism
Receptors, Parathyroid Hormone - metabolism
Signal Transduction - genetics
title Overexpression of parathyroid hormone-related protein or parathyroid hormone in transgenic mice impairs branching morphogenesis during mammary gland development
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