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Molecular Endocrinology Vol. 3, No. 3 503-508
doi:10.1210/mend-3-3-503
Copyright © 1989 by the Endocrine Society.
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The Parathyroid Hormone-Related Protein Associated with Malignancy is Secreted by Neuroendocrine Tumors

L. J. Deftos, A. F. Gazdar, K. Ikeda and A. E. Broadus

Departments of Medicine, University of California, San Diego, San Diego VA Medical Center La Jolla, California 92161
Yale University New Haven, Connecticut 06510
NCI-Navy Medical Oncology Branch, National Cancer Institute and Naval Hospital Bethesda, Maryland 20814

Address requests for reprints to: L. J. Deftos, M.D., V-111C, 3350 La Jolla Village Drive, San Diego, California 92161.

Abstract

We have demonstrated the production of the PTH-related protein (PTHrP) associated with hypercalcemia of malignancy by human neuroendocrine cell lines that also produce calcitonin gene products and chromogranin A. PTHrP was demonstrable in the cells by immunocytochemistry and immunoassay and Northern analysis of the cells revealed the presence of multiple mRNAs for PTHrP. The cell lines also secreted PTHrP in a regulated fashion, with the most potent secretogogue being phorbol. Thus, PTHrP is secreted by neuroendocrine cells and it may have neuroectodermal lineage. The coexpression of calcitonin gene products and chromogranin A, also neuroendocrine, with PTHRP may influence its secretion and ultimate biological effects in vivo.

FOOTNOTES

Supported in part by NIH Grants AR-15888 and CA-49474 (to L.J.D.) and AR-30102 (to A.E.B.), The American Cancer Society (to L.J.D.), the Veterans Administration (to L.J.D.), and by a James Hudson Brown-Alexander B. Coxe Fellowship from the Yale School of Medicine (to K.I.).

Received for publication November 23, 1988. Revision received December 15, 1988. Accepted for publication December 21, 1988.




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