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ASPB 10 insulin induction of increased mitogenic responses and phenotypic changes in human breast epithelial cells: Evidence for enhanced interactions with the insulin‐like growth factor‐I receptor
Author(s) -
Milazzo Giovanni,
Sciacca Laura,
Papa Vincenzo,
Goldfine Ira D.,
Vigneri Riccardo
Publication year - 1997
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/(sici)1098-2744(199701)18:1<19::aid-mc3>3.0.co;2-m
Subject(s) - autophosphorylation , biology , insulin , endocrinology , medicine , insulin receptor , cell culture , growth factor , insulin like growth factor , receptor , insulin receptor substrate , mcf 7 , insulin like growth factor 1 receptor , cancer cell , cancer research , microbiology and biotechnology , insulin resistance , cancer , biochemistry , phosphorylation , human breast , protein kinase a , genetics
The human insulin analogue ASPB 10 has been reported to have increased affinity for the insulin receptor and to cause breast cancer in female rats. In the study reported here, we investigated whether ASPB 10 has an increased mitogenic potency and induces a transformed phenotype in cultured human breast cells. In both MCF‐10 cells (a non‐malignant human breast line) and MCF‐7 cells (a human breast cancer cell line), ASPB 10 was approximately twofold more potent than insulin in competing for 125 I‐insulin binding but sevenfold to tenfold more potent than insulin in competing for 125 I‐insulin‐like growth factor (IGF)‐I binding. In addition, ASPB 10 was twofold more potent than insulin in stimulating insulin receptor autophosphorylation but significantly more potent in stimulating IGF‐I receptor autophosphorylation in both cell lines. Moreover, ASPB 10 was approximately sevenfold more potent than insulin in stimulating the growth of MCF‐10 and MCF‐7 cells. This increased mitogenic effect of ASPB 10 was significantly inhibited (but not abolished) when cells were cultured in the presence of α‐IR3, a monoclonal antibody to the IGF‐I receptor. ASPB 10 , but not insulin, caused phenotypic changes (focus formation) in MCF‐10 cells. Neither agent caused colony formation in soft agar in MCF‐10 cells, but ASPB 10 was more potent than insulin in stimulating colony formation in MCF‐7 cells. These observations indicate that in human breast cells, ASPB 10 has enhanced mitogenic effects and induces phenotypic changes as a consequence of its activation of both insulin and IGF‐I receptors. Mol. Carcinog. 18:19–25, 1997. © 1997 Wiley‐Liss, Inc.