Monoclonal antibody to the type I insulin-like growth factor (IGF-I) receptor blocks IGF-I receptor-mediated DNA synthesis: clarification of the mitogenic mechanisms of IGF-I and insulin in human skin fibroblasts

Journal Article · Sat Feb 01 04:00:00 EST 1986 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.83.3.664· OSTI ID:6469493

Flier, J S; Usher, P; Moses, A C

Insulin and insulin-like growth factor type I (IGF-I) stimulate an overlapping spectrum of biological responses in human skin fibroblasts. Although insulin and IGF-I are known to stimulate the incorporation of (/sup 3/H)thymidine into DNA in these cells, the identify of the receptor(s) that mediates this effect has not been fully clarified. The mouse anti-human IGF-I receptor antibody ..cap alpha..IR-3 binds with specificity to IGF-I but not to insulin receptors in human placental membranes; it also specifically inhibits the binding of /sup 125/I-labeled IGF-I but not /sup 125/I-labeled insulin to suspensions of human skin fibroblasts in a dose-dependent manner. ..cap alpha..IR-3 competitively inhibits IGF-I-mediated stimulation of (/sup 3/H)thymidine incorporation into DNA. This inhibition is dependent on the concentration of ..cap alpha..IR-3 and in the presence of a fixed antibody concentration can be partially overcome by high concentrations of IGF-I. In contrast, at concentrations of < 1 ..mu..g/ml, the effect of insulin to stimulate (/sup 3/H)thymidine incorporation is not inhibited by ..cap alpha..IR-3. However, the incremental effects of higher concentrations (> 1 ..mu..g/ml) of insulin on (/sup 3/H)thymidine incorporation are inhibited by ..cap alpha..IR-3. ..cap alpha..IR-3 is a highly specific antagonist of IGF-I receptor-mediated mitogenesis in human skin fibroblasts. By using this antibody, it is shown directly that insulin can act through the IGF-I receptor to stimulate DNA synthesis but can also activate this effect through the insulin receptor itself.

• Research Organization: Harvard Medical School, Boston, MA
• OSTI ID: 6469493
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 83:3; ISSN PNASA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMAL CELLS
ANIMAL GROWTH
ANIMALS
ANTIBODIES
AZINES
BETA DECAY RADIOISOTOPES
BIOCHEMISTRY
BIOLOGICAL MATERIALS
BIOSYNTHESIS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CHEMISTRY
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DNA
DOSE-RESPONSE RELATIONSHIPS
ELECTRON CAPTURE RADIOISOTOPES
FETAL MEMBRANES
FIBROBLASTS
GROWTH
HETEROCYCLIC COMPOUNDS
HORMONES
INSULIN
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LEUKOCYTES
LIGANDS
LYMPHOCYTES
MAMMALS
MAN
MATERIALS
MEMBRANES
MONOCLONAL ANTIBODIES
NUCLEI
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PEPTIDE HORMONES
PLACENTA
PRIMATES
PYRIMIDINES
RADIOISOTOPES
RADIORECEPTOR ASSAY
RIBOSIDES
SKIN
SOMATIC CELLS
SYNTHESIS
THYMIDINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES