Roles of trk Family Neurotrophin Receptors in Medullary Thyroid Carcinoma Development and Progression
Although initiating mutations in the ret protooncogene have been found in familial and sporadic medullary thyroid carcinoma (MTC), the molecular events underlying subsequent tumor progression stages are unknown. We now report that changes in trk family neurotrophin receptor expression appear to be i...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 96; no. 8; pp. 4540 - 4545 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences of the United States of America
13.04.1999
National Acad Sciences National Academy of Sciences The National Academy of Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | Although initiating mutations in the ret protooncogene have been found in familial and sporadic medullary thyroid carcinoma (MTC), the molecular events underlying subsequent tumor progression stages are unknown. We now report that changes in trk family neurotrophin receptor expression appear to be involved in both preneoplastic thyroid C cell hyperplasia and later tumor progression. Only a subset of normal C cells expresses trk family receptors, but, in C cell hyperplasia, the affected cells consistently express trkB, with variable expression of trkA and trkC. In later stages of gross MTC tumors, trkB expression was substantially reduced, while trkC expression was increased and often intense. In a cell culture model of MTC, exogenous trkB expression resulted in severely impaired tumorigenicity and was associated with 11-fold lower levels of the angiogenesis factor vascular endothelial growth factor. These results suggest that trk family receptor genes participate in MTC development and progression, and, in particular, that trkB may limit MTC tumor growth by inhibition of angiogenesis. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 To whom reprint requests should be addressed at: Oncology Center, Johns Hopkins Medical Institutions, 424 North Bond Street, Baltimore, MD 21231. e-mail: bnelkin@welchlink.welch.jhu.edu. Communicated by Victor A. McKusick, Johns Hopkins Hospital, Baltimore, MD |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.96.8.4540 |