Developmental reprogramming of IGF signaling and susceptibility to endometrial hyperplasia in the rat

Laboratory Investigation; a Journal of Technical Methods and Pathology
Adrienne S McCampbellPeter J A Davies

Abstract

In rodents, a brief neonatal exposure of the developing reproductive tract to the xenoestrogen, diethylstilbestrol (DES) reprograms developing tissues to increase susceptibility to tumorigenesis in adult animals, including uterine adenocarcinoma. Progression from a normal endometrium to carcinoma occurs via the intermediate stage of endometrial hyperplasia. We previously reported that endometrial hyperplasia in postmenopausal women is linked to abnormal insulin-like growth factor-I (IGF-I) signaling. To identify early events involved in the development of hyperplasia in the endometrium, we examined expression and activation of IGF-I pathway components in endometrium of rats exposed to DES. By 5 months of age, 36/60 (60%) of rats exposed to DES on days 3-5 after birth developed endometrial hyperplasia compared to 0% of vehicle-treated controls. Consistent with activation of a mitogenic signaling pathway, Ki67-positive cells increased in DES-exposed endometrium despite compromised ovarian function and hypoestrogenic milieu characteristic of DES-exposed animals. The endometrium of DES-exposed rats overexpressed IGF-II and insulin receptor substrate-1 (IRS-1) and exhibited elevated Akt expression and activation (as judged by phosph...Continue Reading

References

Jan 4, 1979·The New England Journal of Medicine·C M AntunesR Garcia
Feb 1, 1986·American Journal of Epidemiology·N KreigerC A Woolever
Apr 15, 1971·The New England Journal of Medicine·A L HerbstD C Poskanzer
Sep 30, 1994·Annals of the New York Academy of Sciences·J C IrwinL C Giudice
Sep 1, 1997·Proceedings of the Society for Experimental Biology and Medicine·M ShiragaH Fukamachi
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·X WuC L Sawyers
Mar 5, 1999·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·E M Rutanen
Jun 8, 2000·Journal of the National Cancer Institute·G L MutterC Eng
May 1, 1995·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·E.A. WidraJ.P. Palazzo
May 3, 2003·The Journal of Clinical Endocrinology and Metabolism·Lei DengPeter J A Davies
May 22, 2003·Oncology·Eleni PetridouDimitrios Trichopoulos
Oct 21, 2003·Genes, Chromosomes & Cancer·Cheryl Lyn WalkerJeffery I Everitt
Nov 6, 2004·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Jonathan L HechtGeorge L Mutter
May 27, 2005·Maturitas·Sharon A O'TooleDana Seidlova-Wuttke
Jun 7, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jennifer D CookCheryl Lyn Walker
Dec 22, 2005·Nature Reviews. Genetics·Andrew P FeinbergSteven Henikoff
May 20, 2006·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Stefan Karlsson
Jun 17, 2006·Genes & Development·Mei-Ling ChenNissim Hay
Nov 7, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Adrienne S McCampbellPeter J A Davies
Mar 16, 2007·Cell Cycle·Shannon L GibsonLeslie M Shaw

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Citations

Jun 15, 2012·Nature Reviews. Cancer·Cheryl Lyn Walker, Shuk-mei Ho
Feb 27, 2010·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Filiz CayanSaffet Dilek
Jun 30, 2014·Journal of Assisted Reproduction and Genetics·Sevtap KilicT Delibasi
Dec 3, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michaela A OnstadKaren H Lu
Jul 5, 2016·Alcoholism, Clinical and Experimental Research·Catina Crismale-GannWendie S Cohick
Dec 7, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sharmilee Bansal KoretsRobert J Schneider
Aug 28, 2009·Trends in Endocrinology and Metabolism : TEM·Liang Ma

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