PMID: 11920634Mar 29, 2002Paper

Insulin-like growth factor-I has a biphasic effect on colon carcinoma cells through transient inactivation of forkhead1, initially mitogenic, then mediating growth arrest and differentiation

International Journal of Cancer. Journal International Du Cancer
Daina Z EwtonEileen Friedman

Abstract

IGF-I stimulates intestinal cell differentiation after initiating a short proliferative burst, similar to its effect on muscle cell differentiation. Levels of IGF-I attainable in serum (10-20 ng/ml) induced transient growth stimulation of colon carcinoma cells, then growth arrest. When IGF-I functioned as a mitogen, it blocked differentiation. Intestinal cell differentiation occurred once cells had undergone the IGF-I-initiated growth arrest and IGF-I and butyrate acted synergistically to induce maturation markers. IGF-I induces NIH-3T3 cell proliferation and survival by activating the kinase akt, which in turn inhibits various apoptotic mediators and the forkhead family of transcription factors, which mediate expression of p27(kip1). Promoter reporter assays demonstrated that forkhead1 mediates transcription of p27(kip1) in colon carcinoma cells. The mitogenic effects of IGF-I on 4 colon carcinoma cell lines were transient because the inactivating phosphorylation of forkhead1 by akt was short-lived. This allowed transcriptional upregulation of the cdk inhibitor p27(kip1), with a resulting growth arrest. In contrast, in NIH-3T3 cells treated in parallel with identical IGF-I levels, forkhead phosphorylation levels were sustained...Continue Reading

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Citations

Jan 15, 2005·International Journal of Colorectal Disease·Rajaraman DuraiMarc C Winslet
Feb 3, 2012·Breast Cancer Research and Treatment·Lina MuHerbert Yu
Oct 23, 2012·Cancer Letters·Kousuke IshinoHitoshi Nakagama
Sep 3, 2002·American Journal of Respiratory Cell and Molecular Biology·Yuzo KodamaJanet L Martin
May 2, 2009·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·Robert E CarrollTerry G Unterman
Aug 27, 2010·Journal of Surgical Oncology·Hee Eun LeeWoo Ho Kim
May 1, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Megan M GarrityUNKNOWN North Central Cancer Treatment Group
Feb 23, 2017·Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists·Baldomero GonzalezMoisés Mercado
Jul 27, 2007·The Journal of Clinical Endocrinology and Metabolism·Annamaria ColaoGaetano Lombardi
Jul 12, 2019·Frontiers in Endocrinology·Dorota Dworakowska, Ashley B Grossman
Feb 6, 2008·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Elizabeth T JacobsPatricia A Thompson
Jun 12, 2002·The Journal of Biological Chemistry·Geum-Yi KimEileen Friedman

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