Distinctive proliferative phase differences in gene expression in human myometrium and leiomyomata

Wang, Hongbo; Mahadevappa, M.; Yamamoto, Karen K.; Wen, Yan; Chen, Bertha; Warrington, Janet A.; Polan, Mary Lake

doi:10.1016/s0015-0282(03)00730-1

Cited by 73 publications

(65 citation statements)

References 39 publications

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“…For example fibronectin 1, which in our study was significantly upregulated in fibroids with four independent probe sets, has been reported as downregulated in fibroids in a microarray study containing only six fibroid samples (Chegini et al, 2003). The changes in the expression profiles observed between normal myometrium and fibroid tissue also confirmed some previously reported results (Kovacs et al, 2001;Tsibris et al, 2002;Ahn et al, 2003;Chegini et al, 2003;Wang et al, 2003;Weston et al, 2003). For example, CCND1, endothelin receptor type A (EDNRA), collagen type III alpha 1 (COL3A1), and collagen type IV alpha 2 (COL4A2) were upregulated, and early growth response 1 (EGR1), complement component 1r (C1R), actin binding LIM protein 1 (ABLIM1), v-jun sarcoma virus 17 oncogene homolog (JUN), and B-cell CLL/lymphoma 6 (BCL6) were downregulated in fibroids.…”

Section: Discussionsupporting

confidence: 91%

“…DNA microarray analysis has been proven to serve as a useful tool in studying global gene expression in human tumours, and a number of studies have already investigated differences in gene expression levels between normal myometrium and uterine fibroids (Tsibris et al, 2002;Wang et al, 2003;Weston et al, 2003). There are clear differences between the results produced by different microarray experiments on fibroids, although some genes, such as actin binding LIM protein 1, collagen type IV alpha 2, early growth response 1, GATA-binding protein 2, endothelin receptor type A, and c-jun, have been detected as differentially expressed in several studies.…”

Section: Introductionmentioning

confidence: 99%

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7q deletion mapping and expression profiling in uterine fibroids

et al. 2005

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Uterine fibroids are some of the most common tumours of females, but relatively little is known about their molecular basis. Several studies have suggested that deletions on chromosome 7q could have a role in fibroid formation. We analysed 165 sporadic uterine fibroids to define a small 3.2 megabase (Mb) commonly deleted region on 7q22.3-q31.1, flanked by clones AC005070 and AC007567. We also used oligonucleotide microarrays to compare the expression profiles of 10 samples of normal myometrium and 15 fibroids, nine of which displayed 7q-deletions. Activating transcription factor 3, patched homolog (Drosophila), homeo box A5, death-associated protein kinase 1, and retinoic acid receptor responder 3 were downregulated, and excision repair crosscomplementing 3, transcription factor AP-2 gamma and protein kinase C beta 1 were upregulated in fibroids. New pathways were discovered related to fibroid formation. The presence or absence of 7q-deletions did not dramatically affect the global expression pattern of the tumours; changes, however, were observed in genes related to vesicular transport and nucleic acid binding.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

7q deletion mapping and expression profiling in uterine fibroids

et al. 2005

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“…Gene array studies have been conducted to clarify the alteration of gene expression profiles in uterine leiomyoma and have identified numerous genes for which expression is up-or down-regulated compared with levels in normal myometrium (Tsibris et al 2002, Catherino et al 2003, Chegini et al 2003, Skubitz & Skubitz 2003, Wang et al 2003, Weston et al 2003, Hoffman et al 2004, Quade et al 2004. Although the total number of genes analyzed in each array has varied, 5-358 genes per study have been identified as down-regulated in leiomyoma, greatly exceeding the number of up-regulated genes in eight out of nine independent array-based studies (Tsibris et al 2002, Ahn et al 2003, Catherino et al 2003, Chegini et al 2003, Skubitz & Skubitz 2003, Wang et al 2003, Weston et al 2003, Quade et al 2004, Arslan et al 2005.…”

Section: Introductionmentioning

confidence: 99%

“…Although the total number of genes analyzed in each array has varied, 5-358 genes per study have been identified as down-regulated in leiomyoma, greatly exceeding the number of up-regulated genes in eight out of nine independent array-based studies (Tsibris et al 2002, Ahn et al 2003, Catherino et al 2003, Chegini et al 2003, Skubitz & Skubitz 2003, Wang et al 2003, Weston et al 2003, Quade et al 2004, Arslan et al 2005. Downregulated genes would play an important role in leiomyoma phenotype, similar to or more important than up-regulated genes.…”

Section: Introductionmentioning

confidence: 99%

Early growth response gene-1 plays a pivotal role in down-regulation of a cohort of genes in uterine leiomyoma

Ishikawa

Shozu

Okada³

et al. 2007

Journal of Molecular Endocrinology

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Microarray studies have identified many genes that are down-regulated in uterine leiomyoma compared with myometrium, including early growth response gene-1 (EGR1). However, the mechanisms underlying coordinated down-regulation of this gene cohort remain unknown. To address the transcriptional role of EGR1 in leiomyoma, EGR1 binding to promoter sequences on target genes was assessed by chromatin immunoprecipitation (ChIP) assay in leiomyoma tissues and myometrium-derived KW cells. Computer analysis demonstrated that 50 out of 135 genes listed as down-regulated in array reports possessed potential binding sites for EGR1 within 1 kb promoter sequence. ChIP assay was performed for a random selection of 13 genes possessing potential binding sites for EGR1 (Group A), 3 genes known as EGR1 targets in other tissues (Group B), and 4 control genes. Decreased EGR1 bindings were significant for 11 out of 16 genes (Group ACB) in leiomyoma tissues compared with myometrium, and mRNA levels in tissue samples were actually decreased for 7 out of the 11 genes. ChIP analyses performed on KW cells showed induction of EGR1 binding to the promoter region of all genes except one Group ACB gene, but for none of the control genes. These results indicate that EGR1 is a key player in coordinated downregulation of genes in leiomyoma. Application of ChIP-quantitative PCR assay with the aid of computer-assisted analysis of genome databases appears useful for the comprehensive interpretation of array data.

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“…Genomic microarrays have offered novel insights into the pathogenesis of these highly prevalent tumors (1)(2)(3)(4)(5) and have demonstrated both over-and underexpression of numerous genes not previously associated with leiomyomas. Using an Affymetrix U133 platform, (Affymetrix, Santa Clara, CA) our laboratory has noted that genes associated with formation of the extracellular matrix were differentially expressed in the array results (6).…”

Section: Introductionmentioning

confidence: 99%

Comparative ultrastructure of collagen fibrils in uterine leiomyomas and normal myometrium

Leppert

Baginski

Prupas

et al. 2004

Fertility and Sterility

143

130

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Objective-To examine the ultrastructural characteristics of extracellular matrix and mature collagen fibrils in uterine leiomyomas and compare them with those in adjacent normal myometrium.Design-Analysis of paired leiomyoma-myometrium in surgical specimens. Setting-Research center and tertiary care center.Subject(s)-Women undergoing medically indicated hysterectomy for symptomatic uterine leiomyomas. Intervention(s)-None.Main Outcome Measure(s)-Appearance and spatial orientation of the collagen fibrils in leiomyomas compared with myometrium.Result(s)-Observation of specimens at ×12,500 magnification indicated that collagen fibrils were more abundant, loosely packed, and arrayed in a nonparallel manner in leiomyomas compared with myometrium. Random areas were examined at ×6,500 to ×64,000 magnification and revealed collagen fibrils of equal diameter in both leiomyomas and myometrium. However, an ordered and regular barbed appearance was present in collagen fibrils from myometrium but was lacking in leiomyomas. Conclusion(s)-Leiomyomascontain an abnormal collagen fibril structure and orientation, which suggests that the well-regulated fibril formation in myometrium is altered in leiomyomas. Alterations in collagen genes may play a role in the pathogenesis of leiomyomas.

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Distinctive proliferative phase differences in gene expression in human myometrium and leiomyomata

Cited by 73 publications

References 39 publications

7q deletion mapping and expression profiling in uterine fibroids

7q deletion mapping and expression profiling in uterine fibroids

Early growth response gene-1 plays a pivotal role in down-regulation of a cohort of genes in uterine leiomyoma

Comparative ultrastructure of collagen fibrils in uterine leiomyomas and normal myometrium

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