LONGTMR3IGF-I as a more potent alternative to insulin in serum-free culture of HEK293 cells |
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Authors: | Danny Voorhamme Cathernine A Yandell |
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Institution: | (1) Animal Cell Technology, GroPep Ltd., 28 Dalgleish St., 5031 Thebarton, SA, Australia |
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Abstract: | LONGTMR3IGF-I, an analogue of insulin-like growth factor (IGF)-I, was specifically engineered for use in biopharmaceutical protein
production in mammalian cells. LONGTMR3IGF-I is capable of supporting the growth and survival of Chinese hamster ovary cells in serum-free media at concentrations
at least 200-fold lower than required for insulin. LONGTMR3IGF-I also acts as a more potent growth and survival factor than either insulin or native IGF-I in SF culture of human embryonic
kidney (HEK293) cells. To investigate the basis of the enhanced potency of LONGTMR3IGF-I we have examined the mechanism of action of these mitogens in HEK293 cells. All mitogens tested were found to activate
the TypeI IGF receptor (IGF-IR) and insulin receptor (IR) in a dose-responsive manner. However, the level of activation of
both receptors after stimulation with LONGTMR3IGF-I, at lower concentrations, was greater than with either insulin or IGF-I. The greater potency of LONGTMR3IGF-I in activating the IR, despite having a low affinity for IRs, suggests the presence of heterotetrameric IGF-IR/IR dimers.
Interestingly, the decrease in IGF-IR activation at higher concentrations of LONGTMR3IGF-I suggests that the dose-response curve may be bell-shaped. |
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Keywords: | HEK293 cells serum-free culture insulin-like growth factor-I analogue insulin replacement biopharmaceutical protein production |
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