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>Mutant cell line demonstrating a block in insulin and insulin‐like growth factor type 1 (IGF‐1) induced mitogenesis
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Mutant cell line demonstrating a block in insulin and insulin‐like growth factor type 1 (IGF‐1) induced mitogenesis
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机译：Mutant cell line demonstrating a block in insulin and insulin‐like growth factor type 1 (IGF‐1) induced mitogenesis
AbstractRecently, we have isolated a Chinese hamster cell variant (IV‐A1‐j) resistant to an insulin‐diphtheria‐A chain toxic conjugate (Leckett and Germinario: Cytotechnology [in press]. This cell line exhibited a decreased level of insulin binding, but normal growth in serum‐containing medium when compared to the parental cell line (V‐79). In this paper we further demonstrate that while IV‐A1‐j cells are capable of growing in serum‐containing medium, they are insensitive to the mitogenic actions of either insulin or IGF‐1. In contrast, epidermal growth factor (EGF) and/or α‐thrombin (THR) generate a mitogenic effect in IV‐A1‐j cells comparable to that observed in the parental V‐79 cells. The combination of EGF and/or THR with either insulin or IGF‐1 results in an increase in V‐79 cell growth above EGF and/or THR alone. On the other hand, insulin or IGF‐1 in the presence of other mitogens did not stimulate further growth in IV‐A1‐j cells. While insulin binding was lower in IV‐A1‐j cells, internalization of125I‐insulin was not different in the two cell types. Additionally, insulin‐stimulated glycogen synthesis and protein synthesis were not different in the two cell types. These observations are consistent with insulin and IGF‐1 sharing a mitogenic signalling pathway in Chinese hamster fibroblasts and that this pathway is distinct from other growth factor signalling pathways. The fact that this pathway is defective in the IV‐A1‐j cell line indicates the potential usefulness of these cells in identifying a key step(s) in the insul
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