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Evidence for a role of the amyloid precursor protein in thyroid carcinogenesis.
Department of Internal Medicine, University of Leipzig, Ph.-Rosenthal-Str. 27, D-04103 Leipzig, Germany.
Department of Internal Medicine, University of Leipzig, Ph.-Rosenthal-Str. 27, D-04103 Leipzig, Germany.
Institute of Pathology and Neuropathology, University of Duisburg-Essen, Hufelandstraße 55, D-45122 Essen, Germany.
Institute of Pathology, University of Leipzig, Liebigstraße 26, D-04103 Leipzig, Germany.
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2008 (Engelska)Ingår i: The Journal of endocrinology, ISSN 1479-6805, Vol. 198, nr 2, s. 291-9Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

We have recently found an increased expression of amyloid precursor protein (APP) in cold thyroid nodules that are difficult to classify as a truly benign thyroid neoplasm or a lesion with the potential for further dedifferentiation. Since differences in APP activity have been found in other human cancers, we asked whether thyroid carcinogenesis might be associated with an altered APP expression and function. APP regulation was studied in vitro in differentiated (FRTL-5) and dedifferentiated follicular thyroid carcinomas (FTC-133) thyroid cells after specific inhibition or activation of the cAMP-PKA, the PI3K/AKT or the protein kinase c (PKC) cascades. In vivo analysis of APP expression and downstream signalling was performed in benign and malignant thyroid tissues. We found that upregulation of APP expression and sAPP secretion is induced by TSH in differentiated thyroid cells and by insulin in thyroid cancer cells. PKC is a strong activator of APP cleavage and in FTC-133 confers prolonged release of the APP ectodomain. FTC-133 but not FRTL-5 cells show a prominent cell surface expression of the APP ectodomain, which has been suggested to function as an autocrine growth factor. Thyroid cancers are characterized by APP upregulation, increased membrane targeting of the APP ectodomain and significantly increased mRNA levels of the APP scaffold proteins JIP1, ShcA and Fe65.

Ort, förlag, år, upplaga, sidor
2008. Vol. 198, nr 2, s. 291-9
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Medicin och hälsovetenskap
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URN: urn:nbn:se:liu:diva-101882DOI: 10.1677/JOE-08-0005PubMedID: 18480379OAI: oai:DiVA.org:liu-101882DiVA, id: diva2:666776
Tillgänglig från: 2013-11-24 Skapad: 2013-11-24 Senast uppdaterad: 2018-04-25

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