Journal article
Enhancement of insulin-like growth factor signaling in human breast cancer: Estrogen regulation of insulin receptor substrate-1 expression in vitro and in vivo
Molecular endocrinology (Baltimore, Md.), v 13(5), pp 787-796
01 May 1999
PMID: 10319328
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Cross-talk between insulin-like growth factor (IGF)- and estrogen receptor (ER)-signaling pathways results in synergistic growth. We show here that estrogen enhances IGF signaling by inducing expression of three key IGF- regulatory molecules, the type I IGF receptor (IGFR1) and its downstream signaling molecules, insulin receptor substrate (IRS)-1 and IRS-2. Estrogen induction of IGFR1 and IRS expression resulted in enhanced tyrosine phosphorylation of IRS-1 after IGF-I stimulation, followed by enhanced mitogen-activated protein kinase activation. To examine whether these pathways were similarly activated in vivo, we examined MCF-7 cells grown as xenografts in athymic mice. IRS-1 was expressed at high levels in estrogen-dependent growth of MCF-7 xenografts, but withdrawal of estrogen, which decreased tumor growth, resulted in a dramatic decrease in IRS-1 expression. Finally, we have shown that high IRS-1 expression is an indicator of early disease recurrence in ER-positive human primary breast tumors. Taken together, these data not only reinforce the concept of cross-talk between IGF- and ER-signaling pathways, but indicate that IGF molecules may be critical regulators of estrogen-mediated growth and breast cancer pathogenesis.
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Details
- Title
- Enhancement of insulin-like growth factor signaling in human breast cancer: Estrogen regulation of insulin receptor substrate-1 expression in vitro and in vivo
- Creators
- A V Lee - The University of Texas Health Science Center at San AntonioJ G JacksonJ L GoochS G HilsenbeckE Coronado-HeinsohnC K OsborneD Yee
- Publication Details
- Molecular endocrinology (Baltimore, Md.), v 13(5), pp 787-796
- Publisher
- Endocrine Soc
- Number of pages
- 10
- Grant note
- P30CA-54174; P01CA-30195; P50CA-58183-06 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P30CA054174 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000080035700012
- Scopus ID
- 2-s2.0-0033305004
- Other Identifier
- 991021900019004721
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InCites Highlights
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- Web of Science research areas
- Endocrinology & Metabolism