Targeted cellular process profiling approach for uterine leiomyoma using cDNA microarray, proteomics and gene ontology analysis

Abstract

This study utilized both cDNA microarray and two-dimensional protein gel electrophoresis technology to investigate the multiple interactions of genes and proteins involved in uterine leiomyoma pathophysiology. Also, the gene ontology analysis was used to systematically characterize the global expression profiles at cellular process levels. We profiled differentially expressed transcriptome and proteome in six-paired leiomyoma and normal myometrium. Screening up to 17 000 genes identified 21 upregulated and 50 downregulated genes. The gene-expression profiles were classified into mutually dependent 420 functional sets, resulting in 611 cellular processes according to the gene ontology. Also, protein analysis using two-dimensional gel electrophoresis identified 33 proteins (17 upregulated and 16 downregulated) of more than 500 total spots, which was classified into 302 cellular processes. Of these functional profilings, downregulations of transcriptomes and proteoms were shown in cell adhesion, cell motility, organogenesis, enzyme regulator, structural molecule activity and response to external stimulus functional activities that are supposed to play important roles in pathophysiology. In contrast, the upregulation was only shown in nucleic acid-binding activity. Taken together, potentially significant pathogenetic cellular processes were identified and showed that the downregulated functional profiling has a significant impact on the discovery of pathogenic pathway in leiomyoma. Also, the gene ontology analysis can overcome the complexity of expression profiles of cDNA microarray and two-dimensional protein analysis via its cellular process-level approach. Therefore, a valuable prognostic candidate gene with relevance to disease-specific pathogenesis can be found at cellular process levels.

7q deletion mapping and expression profiling in uterine fibroids

“…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.…”

Gene Expression Patterns of Insulin-Like Growth Factor 2 in Human Uterine Fibroid Tissues: A Genetic Study with Clinical Correlations

“…This may suggest that altered imprinting might contribute to the overexpression of this gene. In any case, its overexpression is supported by previous smaller studies reporting the same [15,16,17,25,26]. …”

Expression of insulin-like growth factors (IGFs) and IGF signaling: molecular complexity in uterine leiomyomas

“…Over-expression of IGF-2 in fibroids has been identified in many independent global gene profiling analyses (15)(16)(17)(18)(19)(20)(21). Insulin-like growth factor-2 is one of a few growth factors identified by global transcription profiling as up-regulated, and the level of its over-expression is generally in the range of a two-to threefold increase in fibroids compared with matched myometrium (5).…”

“…The mitogenic role of IGF-1 in fibroid growth has been reported both in vitro and in vivo (10)(11)(12). As a potent mitogenic factor (13), IGF-2 was reported to be overexpressed in fibroids in 1990 (14), and recent global gene transcription profiling analyses have supported the speculation that it is one of few genes constantly over-expressed in fibroids (15)(16)(17)(18)(19)(20)(21). However, the function and regulation (22)(23)(24) of IGF-2 in fibroids are largely unknown.…”