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Antiestrogen ICI 182,780 decreases proliferation of insulin-like growth factor I (IGF-I)-treated MCF-7 cells without inhibiting IGF-I signaling.
Cancer Res. 2002 Jul 15; 62(14):3985-91.CR

Abstract

Previous studies have suggested that antiestrogens inhibit MCF-7 cell proliferation by alteringthe expression or activity of components of the insulin-like growth factor I (IGF-I) signaling pathway, including IGF-I receptor, insulin receptor substrate 1, and phosphatidylinositol 3-kinase. In this report, we examine the effects of the pure antiestrogen ICI 182,780 (ICI) on various targets of IGF-I signaling in MCF-7 cells. ICI treatment led to decreases in the absolute levels of cyclin D1 and cyclin A expression, retinoblastoma protein phosphorylation, and DNA synthesis in IGF-I-treated cells. However, IGF-I retained the ability to induce these events in the presence of ICI, suggesting that ICI treatment did not completely block IGF-I signaling. Consistent with this suggestion, IGF-I-induced phosphorylation of extracellular signal-regulated kinase, AKT, and insulin receptor substrate 1 was unaffected by ICI treatment. Finally, transient expression of either constitutively active phosphatidylinositol 3-kinase or AKT was unable to induce proliferation in ICI-treated MCF-7 cells. Together, these results indicate that ICI can inhibit proliferation without blocking IGF-I signaling and suggest a model in which both estrogen receptor and IGF-I signaling regulate cell cycle components and are required for MCF-7 cell proliferation.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12124331

Citation

Varma, Hemant, and Susan E. Conrad. "Antiestrogen ICI 182,780 Decreases Proliferation of Insulin-like Growth Factor I (IGF-I)-treated MCF-7 Cells Without Inhibiting IGF-I Signaling." Cancer Research, vol. 62, no. 14, 2002, pp. 3985-91.
Varma H, Conrad SE. Antiestrogen ICI 182,780 decreases proliferation of insulin-like growth factor I (IGF-I)-treated MCF-7 cells without inhibiting IGF-I signaling. Cancer Res. 2002;62(14):3985-91.
Varma, H., & Conrad, S. E. (2002). Antiestrogen ICI 182,780 decreases proliferation of insulin-like growth factor I (IGF-I)-treated MCF-7 cells without inhibiting IGF-I signaling. Cancer Research, 62(14), 3985-91.
Varma H, Conrad SE. Antiestrogen ICI 182,780 Decreases Proliferation of Insulin-like Growth Factor I (IGF-I)-treated MCF-7 Cells Without Inhibiting IGF-I Signaling. Cancer Res. 2002 Jul 15;62(14):3985-91. PubMed PMID: 12124331.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antiestrogen ICI 182,780 decreases proliferation of insulin-like growth factor I (IGF-I)-treated MCF-7 cells without inhibiting IGF-I signaling. AU - Varma,Hemant, AU - Conrad,Susan E, PY - 2002/7/19/pubmed PY - 2002/8/14/medline PY - 2002/7/19/entrez SP - 3985 EP - 91 JF - Cancer research JO - Cancer Res VL - 62 IS - 14 N2 - Previous studies have suggested that antiestrogens inhibit MCF-7 cell proliferation by alteringthe expression or activity of components of the insulin-like growth factor I (IGF-I) signaling pathway, including IGF-I receptor, insulin receptor substrate 1, and phosphatidylinositol 3-kinase. In this report, we examine the effects of the pure antiestrogen ICI 182,780 (ICI) on various targets of IGF-I signaling in MCF-7 cells. ICI treatment led to decreases in the absolute levels of cyclin D1 and cyclin A expression, retinoblastoma protein phosphorylation, and DNA synthesis in IGF-I-treated cells. However, IGF-I retained the ability to induce these events in the presence of ICI, suggesting that ICI treatment did not completely block IGF-I signaling. Consistent with this suggestion, IGF-I-induced phosphorylation of extracellular signal-regulated kinase, AKT, and insulin receptor substrate 1 was unaffected by ICI treatment. Finally, transient expression of either constitutively active phosphatidylinositol 3-kinase or AKT was unable to induce proliferation in ICI-treated MCF-7 cells. Together, these results indicate that ICI can inhibit proliferation without blocking IGF-I signaling and suggest a model in which both estrogen receptor and IGF-I signaling regulate cell cycle components and are required for MCF-7 cell proliferation. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/12124331/Antiestrogen_ICI_182780_decreases_proliferation_of_insulin_like_growth_factor_I__IGF_I__treated_MCF_7_cells_without_inhibiting_IGF_I_signaling_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=12124331 DB - PRIME DP - Unbound Medicine ER -