Mitogenic effects of coagulation factor XII and factor XIIa on HepG2 cells

Journal Article · Wed May 15 04:00:00 EDT 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.10.4382· OSTI ID:5933984

Schmeidler-Sapiro, K T; Gordon, E M ^[1]; Ratnoff, O D ^[2]

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1. Univ. of Southern California, Los Angeles (United States)
2. Case Western Reserve Univ. School of Medicine, Cleveland, OH (United States)

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 (10{sup 4} 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 {mu}g/ml) enhanced cell proliferation. Various doses of factor XII enhanced cell proliferation, ({sup 3}H)thymidine incorporation, and ({sup 3}H)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.

• OSTI ID: 5933984
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:10; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACID SEQUENCE
AMINO ACIDS
ANIMAL CELLS
AZINES
BIOLOGICAL EFFECTS
BLOOD COAGULATION FACTORS
CARBOXYLIC ACIDS
COAGULANTS
DISEASES
DNA SEQUENCING
DOSE-RESPONSE RELATIONSHIPS
DRUGS
GROWTH FACTORS
HEMATOLOGIC AGENTS
HEPATOMAS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
LEUCINE
MITOGENS
MOLECULAR STRUCTURE
NEOPLASMS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PROTEINS
PURIFICATION
PYRIMIDINES
RIBOSIDES
STRUCTURAL CHEMICAL ANALYSIS
THYMIDINE
TRITIUM COMPOUNDS
TUMOR CELLS