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Neuroendocrine markers are expressed in human mammary glands
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
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2010 (English)In: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 160, no 1-3, 68-74 p.Article in journal (Refereed) Published
Abstract [en]

Background

Regulatory peptides have previously been detected in epithelial cells of human mammary glands. As these peptides are produced by scattered neuroendocrine cells in the epithelium of other tissues the aim of this study was to investigate whether the mammary glands express molecular markers for neuroendocrine cells.

Material and methods

Specimens from 28 human mammary glands were retrieved. The distribution of immunoreactive cells was determined using immunohistochemistry with antibodies versus a set of endocrine markers including peptide hormones, chromogranins/secretogranins, vesicular monoamine transporters, synaptophysin, serotonin and synaptic vesicle protein 2.

Results

Cells of the luminal epithelium of ducts and lobules of human mammary glands expressed vesicular monoamine transporter 2 and chromogranin B, as well as the previously reported regulatory peptides obestatin, ghrelin, adrenomedullin and apelin. Using consecutive sections, it was revealed that the immunoreactivity patterns of the regulatory peptides and vesicular monoamine transporter 2 were similar. Interestingly, immunoreactivity for secretogranin II, secretogranin III and chromogranin B was identified in myoepithelial cells. No immunoreactivity was detected for chromogranin A or synaptophysin.

Conclusion

Specific cells in the epithelium and myoepithelium of mammary glands express neuroendocrine markers suggesting that mammary glands may have neuroendocrine functions.

Place, publisher, year, edition, pages
2010. Vol. 160, no 1-3, 68-74 p.
Keyword [en]
Breast, Chromogranin, Ghrelin, Obestatin, Secretogranin, Vesicular monoamine transporter
National Category
Medical and Health Sciences
Research subject
Endocrinology and Diabetology
Identifiers
URN: urn:nbn:se:uu:diva-102159DOI: 10.1016/j.regpep.2009.12.011ISI: 000274890000010OAI: oai:DiVA.org:uu-102159DiVA: diva2:344041
Projects
Expression of neuroendocrine markers in normal and neoplastic tissue with an emphasis on ghrelin and obestatin
Available from: 2010-08-17 Created: 2009-05-05 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Expression of Neuroendocrine Markers in Normal and Neoplastic Tissue with an Emphasis on Ghrelin and Obestatin
Open this publication in new window or tab >>Expression of Neuroendocrine Markers in Normal and Neoplastic Tissue with an Emphasis on Ghrelin and Obestatin
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this thesis was to characterize the expression of the peptides ghrelin and obestatin, as well as other neuroendocrine markers in human normal tissues, in invasive breast cancer and a wide panel of neuroendocrine tumors (NETs).

In normal tissues the expression of ghrelin and obestatin was mainly localized to the gastric mucosa, and in lesser extent in the remaining gastrointestinal tract, endocrine pancreas and mammary glands. Double immunofluorescence studies demonstrated that ghrelin and obestatin were co-localized in the same cells displaying the same cytoplasmic distribution.

In normal breast tissue, ghrelin, obestatin, adrenomedullin, apelin and vesicular monoamine transporter 2 were specifically demonstrated in the luminal epithelial cells. Consecutive sections indicated that mammary epithelial cells could express several of these peptides. Secretogranin II and III were also detected in breast tissue, but their presence was restricted to the outer layer of myoepithelial cells, whereas chromogranin B immunoreactivity was found in both the epithelial and myoepithelial cells.

Ghrelin and obestatin immunoreactivity was seen in invasive breast cancer, where the expression could be correlated to factors associated with prognosis. Furthermore, multivariate analysis indicated that ghrelin expression was a possible independent prognostic factor for prolonged recurrence-free and breast cancer-specific survival.

In a panel of NETs and endocrine-related disorders it was revealed that ghrelin and obestatin immunoreactivity was primarily found in tumors originating from the respective normal tissues. The two proteins were detected in only a few cases and only occasional tumor cells were immunoreactive.

In conclusion, ghrelin and obestatin are localized in the gastrointestinal tract, endocrine pancreas and mammary glands. This thesis has contributed to our understanding of the distribution of ghrelin and obestatin in both normal tissue and tumor cells. A potential role of ghrelin as a prognostic factor in invasive breast cancer has been identified and should be further explored.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 64 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 604
Keyword
ghrelin, obestatin, neuroendocrine marker, immunohistochemistry, neuroendocrine tumors, breast cancer, mammary glands
National Category
Medical and Health Sciences
Research subject
Endocrinology and Diabetology
Identifiers
urn:nbn:se:uu:diva-130972 (URN)978-91-554-7909-1 (ISBN)
Public defence
2010-11-20, Enghoffsalen, Ingång 50, Akademiska sjukhuset, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2010-10-28 Created: 2010-09-20 Last updated: 2011-01-13Bibliographically approved

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Grönberg, MalinAmini, Rose-MarieStridsberg, MatsJanson, Eva TiensuuSaras, Jan

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Grönberg, MalinAmini, Rose-MarieStridsberg, MatsJanson, Eva TiensuuSaras, Jan
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