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Mitogenic Effects of Coagulation Factor XII and Factor XIIa on HepG2 Cells

Katherine T. Schmeidler-Sapiro, Oscar D. Ratnoff and Erlinda M. Gordon
Proceedings of the National Academy of Sciences of the United States of America
Vol. 88, No. 10 (May 15, 1991), pp. 4382-4385
Stable URL: http://www.jstor.org/stable/2357048
Page Count: 4
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Mitogenic Effects of Coagulation Factor XII and Factor XIIa on HepG2 Cells
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Abstract

The structure of coagulation factor XII (Hageman factor), inferred from its DNA sequence, includes two epidermal growth factor (EGF)-homologous domains in its amino-terminal region. This suggests that factor XII may exhibit EGF-like activities. Reciprocal antigenic cross-reactivity between factor XII and EGF was shown by exposing purified human factor XII or mouse EGF to anti-mouse EGF or anti-human factor XII. Western blot analysis showed that anti-mouse EGF recognized intact factor XII at 80 kDa. Together, these results suggest that the EGF-homologous domains are accessible for anti-EGF binding in native factor XII. To determine whether factor XII has mitogenic activity, HepG2 or L cells (104 cells per well) were grown in serum-free medium in the presence or absence of factor XII or kaolin-activated factor XII (factor XIIa). Both factors XII and XIIa (6.0 μg/ml) enhanced cell proliferation by ≈2-fold (P < 0.001 and P < 0.005, respectively). In contrast, L cells, which are not EGF target cells, were not affected by either factor XII or factor XIIa. Various doses of factor XII enhanced cell proliferation, [3H]thymidine incorporation, and [3H]leucine incorporation in HepG2 cells cultured under the same conditions. These data indicate that factor XII, like EGF, is a mitogen for HepG2 cells and suggest a possible autocrine role in the liver.

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