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Journal of Clinical Endocrinology & Metabolism Vol. 70, No. 1 149-154
doi:10.1210/jcem-70-1-149
Copyright © 1990 by the Endocrine Society.
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Circulating Fibroblast Growth Factor-Like Substance in Familial Multiple Endocrine Neoplasia Type 1*

M. B. ZIMERING, M. L. BRANDI, D. A. DE GRANGE, S. J. MARX, E. STREETEN, N. KATSUMATA, P. R. MURPHY, Y. SATO, H. G. FRIESEN and G. D. AURBACH

Metabolic Diseases Branch, National Institutes of Diabetes, Digestive and Kidney Diseases, National Institutes of Health (M.B.Z., M.L.B., D.A.d., S.J.M., E.S., G.D.A.) Bethesda, Maryland 20892
The Department of Physiology, University of Manitoba Faculty of Medicine (N.K., P.R.M., Y.S., H.G.F.) Winnipeg, Manitoba, Canada R3E 0W3

Address all correspondence and requests for reprints to Dr. M. B. Zimering, Building 10, Room 9C101, National Institutes of Health, Bethesda, Maryland 20892.

Basic fibroblast growth factor (bFGF) is a potent endothelial cell mitogen found in a variety of normal and tumor tissues. Basic FGF lacks a classical signal sequence, and it is not clear how it is released from cells. bFGF or bFGF-like activity has not been previously demonstrated in plasma. In an earlier study we showed increased mitogenic activity for parathyroidderived epithelial and mesenchymal cells in plasma of subjects with familial multiple endocrine neoplasia type 1 (FMEN1). In the present study we examined the growth-promoting activity of normal and FMENl plasmas [applied to heparin-Sepharose (HS) columns] in parathyroid-derived cloned endothelial cells. FMENl plasma HS-adsorbed activity exceeded normal plasma HS-adsorbed activity in 6 of 8 FMENl plasma samples. Peak (FMENl plasma) HS-adsorbed activity eluted with 0.1–0.3 M NaCl, was completely neutralized by specific antibodies against bFGF, and had an apparent mol wt of 110 kD. Active fractions from FMENl plasma prepared by gel filtration in 7 M urea displayed apparent mol wt of about 14–16 kD and showed increased apparent affinity for HS; recovered activity appeared principally in the 3.0-M NaCl eluate. Using a sensitive two-site immunoradiometric assay for bFGF we found 0.4 ng/mL bFGFlike immunoreactivity in the highly purified 3.0-M NaCl eluate from a HS column to which the active components from gel filtration of FMENl plasma in 7 M urea were applied. These results imply that bFGF or closely related factors circulate in FMENl.

* This work was supported in part by the NCI of Canada and the Medical Research Council of Canada.

Received June 20, 1989.




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