Development of a novel insulin receptor (IR) antagonist that exhibits anti-breast tumor activity

Human Cell
Kuang WenbinZhu Shuangjiu

Abstract

Many reports have indicated that the insulin receptor (IR) causes tumorigenesis and the development of breast cancer. It has been considered a potential target for treating IR-related tumors. Traditionally, there are two categories of insulin receptor (IR) antagonists, they are small molecule antagonists and anti-IR antibodies. Here, we describe a new method (anti-idiotypic antibody strategy) for the development of IR antagonist. Hybridoma technology was employed to design and identify a series of anti-idiotypic antibodies against insulin. After repeated screening and identification, an anti-idiotypic antibody against IR (AK98) was obtained. Analysis through competitive ELISA and competitive receptor binding indicated that AK98 mimicked the receptor binding epitope of insulin. The interaction between AK98 and IR was determined using indirect immunofluorescence, immunoelectron microscopy, and Immunoprecipitation-Western (IP-WB). Further research using a tumor cell model revealed that AK98 inhibited insulin-IR binding and IR-mediated intracellular signaling pathways. Conclusively, the main purpose of this paper is that we proposed a new method (anti-idiotypic antibody strategy) to develop the insulin receptor (IR) antagonist (AK9...Continue Reading

References

Jan 1, 1983·Journal of Cellular Biochemistry·Y ShechterI R Cohen
Mar 1, 2005·Trends in Endocrinology and Metabolism : TEM·Leona PlumJens C Brüning
Oct 24, 2006·Nature Reviews. Molecular Cell Biology·Philip Cohen
May 25, 2011·Endocrine-related Cancer·Antonino Belfiore, Roberta Malaguarnera
Feb 22, 2012·Nature Medicine·Mingjian LuMorris J Birnbaum
Sep 16, 2015·The International Journal of Biochemistry & Cell Biology·Hainan LanSteven Li
Jul 3, 2016·Journal of Endocrinological Investigation·R VigneriL Frittitta

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Methods Mentioned

BETA
ELISA
flow cytometry
fluorescence imaging
transmission electron microscopy
transfection
confocal microscopy
biosensor
chip
chips

Software Mentioned

SPSS25

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