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

Peng, Lan; Ye, Wen; Han, Yi; Wei, Anran; Shi, Guizhi; Mizuguchi, Masashi; Lee, Peng; Hernando, Eva; Mittal, Khush; Wei, Jian Jun

doi:10.1016/j.fertnstert.2007.10.083

Cited by 50 publications

(44 citation statements)

References 44 publications

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“…These include IGF-1 (72,73), platelet-derived growth factor (PDGF) (71), vascular endothelial growth factor (VEGF) (74), EGF (75) and fibroblast growth factor (FGF) (76). Figure 2 presents a simplified illustration of growth factor signaling.…”

Section: Growth Factor Signalingmentioning

confidence: 99%

“…Several studies point to a role for IGFs in leiomyoma pathobiology. For example, Peng and colleagues (73) found that one third of uterine leiomyomas demonstrate dysregulation in IGFs. They obtained uterine leiomyoma samples from hysterectomy cases and performed microarray analysis, immunohistochemistry, RT-PCR, methylation analysis and Western blotting.…”

Section: Role Of Individual Growth Factors In Leiomyoma Pathobiologymentioning

confidence: 99%

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Signaling Pathways in Leiomyoma: Understanding Pathobiology and Implications for Therapy

Borahay

Al-Hendy

Kılıç

et al. 2015

Mol Med

129

147

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Uterine leiomyomas are the most common tumors of the female genital tract, affecting 50% to 70% of females by the age of 50. Despite their prevalence and enormous medical and economic impact, no effective medical treatment is currently available. This is, in part, due to the poor understanding of their underlying pathobiology. Although they are thought to start as a clonal proliferation of a single myometrial smooth muscle cell, these early cytogenetic alterations are considered insufficient for tumor development and additional complex signaling pathway alterations are crucial. These include steroids, growth factors, transforming growth factor-beta (TGF-β)/Smad; wingless-type (Wnt)/β-catenin, retinoic acid, vitamin D, and peroxisome proliferator-activated receptor γ (PPARγ). An important finding is that several of these pathways converge in a summative way. For example, mitogen-activated protein kinase (MAPK) and Akt pathways seem to act as signal integrators, incorporating input from several signaling pathways, including growth factors, estrogen and vitamin D. This underlines the multifactorial origin and complex nature of these tumors. In this review, we aim to dissect these pathways and discuss their interconnections, aberrations and role in leiomyoma pathobiology. We also aim to identify potential targets for development of novel therapeutics.

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Section: Growth Factor Signalingmentioning

confidence: 99%

Section: Role Of Individual Growth Factors In Leiomyoma Pathobiologymentioning

confidence: 99%

Signaling Pathways in Leiomyoma: Understanding Pathobiology and Implications for Therapy

Borahay

Al-Hendy

Kılıç

et al. 2015

Mol Med

129

147

View full text Add to dashboard Cite

show abstract

“…Growth factors such as EGF, VEGF, and PDGF are known to be significant contributors to the development and growth of uterine leiomyomas (25,26,28,39,40). To investigate the effects of simvastatin on the Ras/Raf/MEK/ERK pathway, we treated HuLM cells with different simvastatin concentrations for 48 h and monitored ERK phosphorylation.…”

Section: Simvastatin Inhibits the Proliferation Of Leiomyoma Cells-mentioning

confidence: 99%

Simvastatin Potently Induces Calcium-dependent Apoptosis of Human Leiomyoma Cells

Borahay

Kılıç

Yallampalli

et al. 2014

Journal of Biological Chemistry

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Background: Statins have broad-reaching effects beyond lowering plasma lipids, including antitumor properties. Results: Simvastatin inhibits proliferation and induces calcium-dependent apoptosis of human uterine leiomyoma cells. Conclusion:We report a novel calcium-mediated pathway associated with antitumor properties of simvastatin. Significance: Simvastatin may have antitumor properties significant for the treatment of human uterine leiomyomas.

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“…Of all growth factors, the role of IGF-2 appears most prominent in uterine leiomyoma. It is involved in the growth of fibroid tumors through endocrine, autocrine and paracrine stimulation of cellular differentiation [13,14,15]. Several studies have focused on the description of IGF-2 gene activity in fibroid tissue.…”

Section: Introductionmentioning

confidence: 99%

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

Csatlós¹,

Rigó²,

Laky³

et al. 2013

Gynecol Obstet Invest

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Background/Aims: We investigated insulin-like growth factor 2 (IGF-2) gene activity in human uterine fibroid tissue. Results of the genetic testing were correlated with clinical data. Methods: We obtained samples from patients treated for uterine fibroid and from patients undergoing hysterectomy due to other indications (control group). The examined group (with fibroid) contained 101 cases, while the control group was similar with 110 patients. Gene expression values were determined using the standard PCR technique. Clinical data were available from the computer database of the department. Results: IGF-2 gene expression was significantly higher in the fibroid group. There was no correlation between increase in gene activity and the number of tumors. History of previous uterine fibroid did not seem to predict IGF-2 gene activity in the current fibroid tumor tissue. IGF-2 gene expression did not correlate with cumulative duration of lactation following prior pregnancies. Conclusion: IGF-2 gene activity is significantly increased in leiomyoma tissue compared to normal myometrium. Familial aggregation of uterine fibroids is not significantly associated with increased IGF-2 gene activity; other genes may have a stronger etiological role. It appears that the genetic factors potentially important in the development of familiar uterine leiomyoma are not related to the IGF-2 gene.

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

Cited by 50 publications

References 44 publications

Signaling Pathways in Leiomyoma: Understanding Pathobiology and Implications for Therapy

Signaling Pathways in Leiomyoma: Understanding Pathobiology and Implications for Therapy

Simvastatin Potently Induces Calcium-dependent Apoptosis of Human Leiomyoma Cells

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

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