title: Estrogen-induced changes in IGF-I, Myb family and MAP kinase pathway genes in human uterine leiomyoma and normal uterine smooth muscle cell lines.
abstract: Many studies have implicated numerous hormones, growth factors, cytokines and other signal transduction molecules in the pathogenesis of uterine leiomyoma. Estrogen and estrogen-related genes are thought to play a key role in the growth of uterine leiomyomas, but the molecular mechanisms are unclear. In an attempt to investigate various pathways that might be involved in estrogen-regulated uterine leiomyoma growth as well as to identify any novel effector genes, microarray studies comparing estrogen-treated uterine leiomyoma cells (UtLM) and normal myometrial cells to untreated cells were performed. Several genes were differentially expressed in estrogen treated UtLM cells, including insulin-like growth factor-I (IGF-I) and others potentially involved in the IGF-I signalling pathway, specifically genes for A-myb, a transcription factor which promotes cell cycle progression and for MKP-1, a dual specificity phosphatase that dephosphorylates mitogen-activated protein kinase. IGF-I and A-myb were up-regulated in estrogen-treated cells while MKP-1 was down-regulated. Two other cell cycle promoting genes, c-fos and myc, were also down-regulated in estrogen treated UtLM cells. These genes are typically up-regulated in response to estrogen in some cells, notably breast epithelial cells, yet consistently have lower expression levels in uterine leiomyoma tissue when compared to autologous myometrium. Our results demonstrate some novel genes that may play a role in the growth of uterine leiomyoma, strengthen the case for involvement of the IGF-I pathway in the response of UtLM to estrogen and corroborate evidence that uterine smooth muscle cells respond to estrogen with a different gene expression pattern than that seen in epithelial cells.
authors.affiliation: Laboratory of Experimental Pathology and Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Swartz
authors.forename: C A
authors.initials: CA
authors.lastname: Afshari
authors.forename: L
authors.initials: L
authors.lastname: Yu
authors.forename: K E
authors.initials: KE
authors.lastname: Hall
authors.forename: D
authors.initials: D
authors.lastname: Dixon
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics; D054638:Dual Specificity Phosphatase 1; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D007889:Leiomyoma / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010749:Phosphoprotein Phosphatases / Q000235:genetics; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D014594:Uterine Neoplasms / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014599:Uterus / Q000166:cytology
chemical_list: D018797:Cell Cycle Proteins; D004967:Estrogens; D017874:Immediate-Early Proteins; C088831:MYBL1 protein, human; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D007334:Insulin-Like Growth Factor I; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; D017027:Protein Tyrosine Phosphatases