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R. ILONA LINNOILA and
JAMES F. BATTEY
Uniformed Services University of the Health Sciences, Department of Defense (F.C.), and the National Cancer Institute-Navy Medical Oncology Branch, Division of Cancer Treatment, National Cancer Institute and National Naval Medical Center (J.F., J.G., A.-M.L.-Y., R.I.L., J.F.B.) Bethesda, Maryland 20814
Address requests for reprints to: Dr. Frank Cuttitta, National Cancer Institute, Navy Medical Oncology Branch, National Naval Medical Center, Bethesda, Maryland 20814.
Mammalian gastrin-releasing peptide (GRP) is found in cells of neuroendocrine and neural origin, and GRP mediates a variety of physiological and trophic responses when it binds to high affinity cell surface receptors on effector cells. Analysis of cDNA clones derived from prepro-GRP mRNAs predict the concurrent expression of a unique series of peptide hormones, the GRP gene-associated peptides (GGAPs). Alternative RNA splicing of the primary GRP gene transcript results in mRNAs that could encode 3 distinct forms of GGAPs. Using specific antisera directed against synthetic peptides representing portions of the predicted GGAPs, we found multiple GGAP forms in the endocrine cells of human fetal lung and in human small cell lung cancer cells (SCLC). Within a single pulmonary endocrine cell, at least 2 of these 3 predicted forms could be demonstrated using immunohistochemical techniques. In addition, concordant expression of GRP and GGAPs was found in 10 SCLC cell lines and 3 human SCLC tumors. These findings establish GGAPs as a novel peptide family in man and warrant further investigation into their potential role in normal and malignant growth.
* The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Navy or the Department of Defense.
Permanent Research Associate from the Fonds National de la Recherche Scientifique (Belgium), partially supported by a European Organization for Research on Treatment of Cancer fellowship at the NCI.
Received October 8, 1987.
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