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AMG 479, a Novel IGF-1-R Antibody, Inhibits Endometrial Cancer Cell Proliferation Through Disruption of the PI3K/Akt and MAPK Pathways

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Abstract

Our goal was to evaluate the therapeutic potential of a novel antibody to the insulin growth factor-1 receptor (IGF-1-R; AMG 479) in endometrial cancer cells. The endometrial cancer cell lines, ECC-1/PRAB72 and RL-95-2, were used. Treatment with AMG 479 (0.02-200 nmol/L) resulted in inhibition of cell proliferation at 72 to 120 hours. Insulin growth factor-1 (0.15-7.5 nmol/L) stimulated growth in both cell lines (range of 15%-42%,P = .0025-.0445), which could be blocked by pretreatment with AMG 479 (mean of 29% for ECC-1/PRAB72,P = .006-.007; mean of 36% for RL-95-2,P = .0002-.0045). AMG 479 suppressed IGF-1-R kinase activity in a dose-dependent manner. Cells treated with AMG 479 underwent either G1 (ECC-1/PRAB72) or G2 (RL-95-2) arrest. AMG 479 decreased human telomerase reverse transcriptase (hTERT) mRNA expression in both endometrial cancer cell lines. Treatment with AMG 479 rapidly blocked IGF-1-induced phosphorylation of IFG-1-R, Akt, and p44/42. Thus, manipulation of the IGF-1-R pathway may serve as a promising therapeutic strategy for the treatment of endometrial cancer.

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Author notes

  1. This author contributed an equal amount of work as first author

Authors and Affiliations

  1. Gynecologic Oncology Associates, CA, Newport Beach, USA

    Albert Mendivil MD

  2. University of North Carolina, Division of Gynecologic Oncology, CB #7572, 27599, NC, Chapel Hill, USA

    Chunxiao Zhou MD, PhD, Paola A. Gehrig MD, Kim M. Malloy MS & Victoria L. Bae-Jump MD, PhD

  3. University of Virginia, Division of Gynecologic Oncology, VA, Charlottesville, USA

    Leigh A. Cantrell MD, MPH

  4. Department of Obstetrics and Gynecology, Erasmus University Medical Center, Rotterdam, The Netherlands

    Leen J. Blok PhD & Curt W. Burger MD, PhD

Authors
  1. Albert Mendivil MD
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  2. Chunxiao Zhou MD, PhD
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  3. Leigh A. Cantrell MD, MPH
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  4. Paola A. Gehrig MD
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  5. Kim M. Malloy MS
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  6. Leen J. Blok PhD
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  7. Curt W. Burger MD, PhD
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  8. Victoria L. Bae-Jump MD, PhD
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Corresponding author

Correspondence to Victoria L. Bae-Jump MD, PhD.

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Mendivil, A., Zhou, C., Cantrell, L.A. et al. AMG 479, a Novel IGF-1-R Antibody, Inhibits Endometrial Cancer Cell Proliferation Through Disruption of the PI3K/Akt and MAPK Pathways. Reprod. Sci. 18, 832–841 (2011). https://doi.org/10.1177/1933719111398501

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  • DOI: https://doi.org/10.1177/1933719111398501

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