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Research Article

Insulin-like growth factor II mediates epidermal growth factor-induced mitogenesis in cervical cancer cells

M A Steller, C H Delgado, and Z Zou
PNAS December 19, 1995 92 (26) 11970-11974; https://doi.org/10.1073/pnas.92.26.11970
M A Steller
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C H Delgado
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Z Zou
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Abstract

There is increasing evidence that activation of the insulin-like growth factor I (IGF-I) receptor plays a major role in the control of cellular proliferation of many cell types. We studied the mitogenic effects of IGF-I, IGF-II, and epidermal growth factor (EGF) on growth-arrested HT-3 cells, a human cervical cancer cell line. All three growth factors promoted dose-dependent increases in cell proliferation. In untransformed cells, EGF usually requires stimulation by a "progression" factor such as IGF-I, IGF-II, or insulin (in supraphysiologic concentrations) in order to exert a mitogenic effect. Accordingly, we investigated whether an autocrine pathway involving IGF-I or IGF-II participated in the EGF-induced mitogenesis of HT-3 cells. With the RNase protection assay, IGF-I mRNA was not detected. However, IGF-II mRNA increased in a time-dependent manner following EGF stimulation. The EGF-induced mitogenesis was abrogated in a dose-dependent manner by IGF-binding protein 5 (IGFBP-5), which binds to IGF-II and neutralizes it. An antisense oligonucleotide to IGF-II also inhibited the proliferative response to EGF. In addition, prolonged, but not short-term, stimulation with EGF resulted in autophosphorylation of the IGF-I receptor, and coincubations with both EGF and IGFBP-5 attenuated this effect. These data demonstrate that autocrine secretion of IGF-II in HT-3 cervical cancer cells can participate in EGF-induced mitogenesis and suggest that autocrine signals involving the IGF-I receptor occur "downstream" of competence growth factor receptors such as the EGF receptor.

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Insulin-like growth factor II mediates epidermal growth factor-induced mitogenesis in cervical cancer cells
M A Steller, C H Delgado, Z Zou
Proceedings of the National Academy of Sciences Dec 1995, 92 (26) 11970-11974; DOI: 10.1073/pnas.92.26.11970

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Insulin-like growth factor II mediates epidermal growth factor-induced mitogenesis in cervical cancer cells
M A Steller, C H Delgado, Z Zou
Proceedings of the National Academy of Sciences Dec 1995, 92 (26) 11970-11974; DOI: 10.1073/pnas.92.26.11970
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