Insulinlike growth factor-binding protein modulates the growth response to insulinlike growth factor 1 by human gastric cancer cells

Yan Shi Guo, R. Daniel Beauchamp, Gui Fang Jin, Courtney Townsend, James C. Thompson

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background: This study determined whether the resistance to the mitogenic effect of insulinlike growth factor 1 (IGF-1) in AGS (we found that IGF-1 had almost no effect on the growth of AGS) cells is caused by the absence of IGF-1 receptor on the cells or by the interference of endogenous IGFs and IGF-binding protein (IGFBP). Methods: IGF-1 receptors were examined by radioligand binding assay. The protein in conditioned medium and the molecular weight of IGF-1 receptors on AGS cells were determined by affinity cross-linking with 125I-IGF-1 followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Messenger RNAs for IGF-1, IGF-2, and IGFBP-4 were detected by Northern analysis. Results: AGS cells possessed a single class of high-affinity binding sites for IGF-1 (dissociation constant [Kd], 0.51), with a binding capacity ~ 4 × 104 sites per cell. The size of the α subunit of IGF-1 receptors on cell membranes was ~ 130 kilodaltons. des(1-3) IGF-1, a truncated IGF-1 with very low affinity to IGFBPs, stimulated AGS cell growth in dose-dependent fashion. The medium conditioned by AGS cells contained IGFBPs of 27-32 and 37-42 kilodaltons. AGS cells expressed messenger (mRNA) RNAs for IGF-2 and IGFBP-4 but not for IGF-1, whereas another gastric carcinoma cell line (SIIA), whose growth is stimulated by IGF-1, expressed mRNA IGF-2 but did not express mRNA for IGF-1 or IGFBP-4: Conclusions: The relative absence of growth response of AGS cells to IGF-1 is due to the endogenously produced IGFBPs sequestering IGF-1 and preventing receptor interaction.

Original languageEnglish (US)
Pages (from-to)1595-1604
Number of pages10
JournalGastroenterology
Volume104
Issue number6
StatePublished - 1993

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Stomach Neoplasms
Intercellular Signaling Peptides and Proteins
Carrier Proteins
Growth
Insulin-Like Growth Factor Binding Proteins
Growth Factor Receptors
Insulin-Like Growth Factor Binding Protein 4
Insulin-Like Growth Factor II
Messenger RNA
Conditioned Culture Medium
Radioligand Assay
Sodium Dodecyl Sulfate
Polyacrylamide Gel Electrophoresis
Stomach
Molecular Weight
Binding Sites
Cell Membrane
Carcinoma
Cell Line

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Insulinlike growth factor-binding protein modulates the growth response to insulinlike growth factor 1 by human gastric cancer cells. / Guo, Yan Shi; Beauchamp, R. Daniel; Jin, Gui Fang; Townsend, Courtney; Thompson, James C.

In: Gastroenterology, Vol. 104, No. 6, 1993, p. 1595-1604.

Research output: Contribution to journalArticle

Guo, Yan Shi ; Beauchamp, R. Daniel ; Jin, Gui Fang ; Townsend, Courtney ; Thompson, James C. / Insulinlike growth factor-binding protein modulates the growth response to insulinlike growth factor 1 by human gastric cancer cells. In: Gastroenterology. 1993 ; Vol. 104, No. 6. pp. 1595-1604.
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T1 - Insulinlike growth factor-binding protein modulates the growth response to insulinlike growth factor 1 by human gastric cancer cells

AU - Guo, Yan Shi

AU - Beauchamp, R. Daniel

AU - Jin, Gui Fang

AU - Townsend, Courtney

AU - Thompson, James C.

PY - 1993

Y1 - 1993

N2 - Background: This study determined whether the resistance to the mitogenic effect of insulinlike growth factor 1 (IGF-1) in AGS (we found that IGF-1 had almost no effect on the growth of AGS) cells is caused by the absence of IGF-1 receptor on the cells or by the interference of endogenous IGFs and IGF-binding protein (IGFBP). Methods: IGF-1 receptors were examined by radioligand binding assay. The protein in conditioned medium and the molecular weight of IGF-1 receptors on AGS cells were determined by affinity cross-linking with 125I-IGF-1 followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Messenger RNAs for IGF-1, IGF-2, and IGFBP-4 were detected by Northern analysis. Results: AGS cells possessed a single class of high-affinity binding sites for IGF-1 (dissociation constant [Kd], 0.51), with a binding capacity ~ 4 × 104 sites per cell. The size of the α subunit of IGF-1 receptors on cell membranes was ~ 130 kilodaltons. des(1-3) IGF-1, a truncated IGF-1 with very low affinity to IGFBPs, stimulated AGS cell growth in dose-dependent fashion. The medium conditioned by AGS cells contained IGFBPs of 27-32 and 37-42 kilodaltons. AGS cells expressed messenger (mRNA) RNAs for IGF-2 and IGFBP-4 but not for IGF-1, whereas another gastric carcinoma cell line (SIIA), whose growth is stimulated by IGF-1, expressed mRNA IGF-2 but did not express mRNA for IGF-1 or IGFBP-4: Conclusions: The relative absence of growth response of AGS cells to IGF-1 is due to the endogenously produced IGFBPs sequestering IGF-1 and preventing receptor interaction.

AB - Background: This study determined whether the resistance to the mitogenic effect of insulinlike growth factor 1 (IGF-1) in AGS (we found that IGF-1 had almost no effect on the growth of AGS) cells is caused by the absence of IGF-1 receptor on the cells or by the interference of endogenous IGFs and IGF-binding protein (IGFBP). Methods: IGF-1 receptors were examined by radioligand binding assay. The protein in conditioned medium and the molecular weight of IGF-1 receptors on AGS cells were determined by affinity cross-linking with 125I-IGF-1 followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Messenger RNAs for IGF-1, IGF-2, and IGFBP-4 were detected by Northern analysis. Results: AGS cells possessed a single class of high-affinity binding sites for IGF-1 (dissociation constant [Kd], 0.51), with a binding capacity ~ 4 × 104 sites per cell. The size of the α subunit of IGF-1 receptors on cell membranes was ~ 130 kilodaltons. des(1-3) IGF-1, a truncated IGF-1 with very low affinity to IGFBPs, stimulated AGS cell growth in dose-dependent fashion. The medium conditioned by AGS cells contained IGFBPs of 27-32 and 37-42 kilodaltons. AGS cells expressed messenger (mRNA) RNAs for IGF-2 and IGFBP-4 but not for IGF-1, whereas another gastric carcinoma cell line (SIIA), whose growth is stimulated by IGF-1, expressed mRNA IGF-2 but did not express mRNA for IGF-1 or IGFBP-4: Conclusions: The relative absence of growth response of AGS cells to IGF-1 is due to the endogenously produced IGFBPs sequestering IGF-1 and preventing receptor interaction.

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