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Estrogen Regulates MAPK-Related Genes through Genomic and Nongenomic Interactions between IGF-I Receptor Tyrosine Kinase and Estrogen Receptor-Alpha Signaling Pathways in Human Uterine Leiomyoma Cells
Joint Authors
Dixon, Darlene
Yu, Linda
Kissling, Grace E.
Klippel, Michelle
Huynh, Hoang-Long C.
Gao, Xiaohua
Castro, Lysandra
Flagler, Norris D.
Lu, Yi
Moore, Alicia B.
Source
Journal of Signal Transduction
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-10-09
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
Estrogen and growth factors play a major role in uterine leiomyoma (UtLM) growth possibly through interactions of receptor tyrosine kinases (RTKs) and estrogen receptor-alpha (ERα) signaling.
We determined the genomic and nongenomic effects of 17β-estradiol (E2) on IGF-IR/MAPKp44/42 signaling and gene expression in human UtLM cells with intact or silenced IGF-IR.
Analysis by RT2 Profiler PCR-array showed genes involved in IGF-IR/MAPK signaling were upregulated in UtLM cells by E2 including cyclin D kinases, MAPKs, and MAPK kinases; RTK signaling mediator, GRB2; transcriptional factors ELK1 and E2F1; CCNB2 involved in cell cycle progression, proliferation, and survival; and COL1A1 associated with collagen synthesis.
Silencing (si)IGF-IR attenuated the above effects and resulted in upregulation of different genes, such as transcriptional factor ETS2; the tyrosine kinase receptor, EGFR; and DLK1 involved in fibrosis.
E2 rapidly activated IGF-IR/MAPKp44/42 signaling nongenomically and induced phosphorylation of ERα at ser118 in cells with a functional IGF-IR versus those without.
E2 also upregulated IGF-I gene and protein expression through a prolonged genomic event.
These results suggest a pivotal role of IGF-IR and possibly other RTKs in mediating genomic and nongenomic hormone receptor interactions and signaling in fibroids and provide novel genes and targets for future intervention and prevention strategies.
American Psychological Association (APA)
Yu, Linda& Moore, Alicia B.& Castro, Lysandra& Gao, Xiaohua& Huynh, Hoang-Long C.& Klippel, Michelle…[et al.]. 2012. Estrogen Regulates MAPK-Related Genes through Genomic and Nongenomic Interactions between IGF-I Receptor Tyrosine Kinase and Estrogen Receptor-Alpha Signaling Pathways in Human Uterine Leiomyoma Cells. Journal of Signal Transduction،Vol. 2012, no. 2012, pp.1-12.
https://search.emarefa.net/detail/BIM-454233
Modern Language Association (MLA)
Yu, Linda…[et al.]. Estrogen Regulates MAPK-Related Genes through Genomic and Nongenomic Interactions between IGF-I Receptor Tyrosine Kinase and Estrogen Receptor-Alpha Signaling Pathways in Human Uterine Leiomyoma Cells. Journal of Signal Transduction No. 2012 (2012), pp.1-12.
https://search.emarefa.net/detail/BIM-454233
American Medical Association (AMA)
Yu, Linda& Moore, Alicia B.& Castro, Lysandra& Gao, Xiaohua& Huynh, Hoang-Long C.& Klippel, Michelle…[et al.]. Estrogen Regulates MAPK-Related Genes through Genomic and Nongenomic Interactions between IGF-I Receptor Tyrosine Kinase and Estrogen Receptor-Alpha Signaling Pathways in Human Uterine Leiomyoma Cells. Journal of Signal Transduction. 2012. Vol. 2012, no. 2012, pp.1-12.
https://search.emarefa.net/detail/BIM-454233
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-454233