Protein Expression of Estrogen Receptors α and β and Aromatase in Myometrium and Uterine Leiomyoma

Grings, Anelise Olmos; Lora, Vanessa; Ferreira, Gustavo Dias; Brum, Ilma Simoni; Corleta, Helena von Eye; Capp, Edison

doi:10.1159/000330700

Cited by 32 publications

(13 citation statements)

References 46 publications

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“…Several studies found that mRNA and protein expression levels as well as the content of ER- α and ER- β are higher in leiomyoma compared to those in normal myometrium [66, 67]. According to their hypothesis, estrogens may exert their growth-stimulatory effects on leiomyomas intermediated by cytokines, growth factors, or apoptosis factors [68]. Ishikawa et al [69] suggested that estrogens can maintain progesterone receptor (PR) levels, and thus progesterone through its receptor may promote leiomyoma growth.…”

Section: Pathogenesis Of Uterine Leiomyomamentioning

confidence: 99%

Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

Ciavattini

Giuseppe

Stortoni

et al. 2013

Obstetrics and Gynecology International

167

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Uterine leiomyomas (fibroids or myomas) are benign tumors of uterus and clinically apparent in a large part of reproductive aged women. Clinically, they present with a variety of symptoms: excessive menstrual bleeding, dysmenorrhoea and intermenstrual bleeding, chronic pelvic pain, and pressure symptoms such as a sensation of bloatedness, increased urinary frequency, and bowel disturbance. In addition, they may compromise reproductive functions, possibly contributing to subfertility, early pregnancy loss, and later pregnancy complications. Despite the prevalence of this condition, myoma research is underfunded compared to other nonmalignant diseases. To date, several pathogenetic factors such as genetics, microRNA, steroids, growth factors, cytokines, chemokines, and extracellular matrix components have been implicated in the development and growth of leiomyoma. This paper summarizes the available literature regarding the ultimate relative knowledge on pathogenesis of uterine fibroids and their interactions with endometrium and subendometrial myometrium.

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Section: Pathogenesis Of Uterine Leiomyomamentioning

confidence: 99%

Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

Ciavattini

Giuseppe

Stortoni

et al. 2013

Obstetrics and Gynecology International

167

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“…The abnormal proliferation of smooth muscle cells seen in fibroid tissue is due to several factors, including an increased sensitivity to estrogens and higher levels of various growth factors including insulin-like growth factors 1 and 2 (IGF-1, IGF-2), transforming growth factor beta, epidermal growth factor, basic fibroblast growth factor and genes [9,10,11]. …”

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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“…The basis of this marked health disparity is not very clear. Potential etiologies of uterine fibroids including correlation to metabolic syndrome and genetic factors have been investigated [6,7,8]. We have recently identified two genetic polymorphisms in estrogen receptor-α and catechol- o -methyltransferase (COMT) genes that are associated with uterine fibroids and are more prevalent in African Americans [9,10].…”

Section: Introductionmentioning

confidence: 99%

Green Tea Extract Inhibition of Human Leiomyoma Cell Proliferation Is Mediated via Catechol-<b><i>O</i></b>-Methyltransferase

Zhang

Rajaratnam

Al-Hendy

et al. 2014

Gynecol Obstet Invest

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Background/Aims: To investigate the inhibitory effect of green tea extract, epigallocatechin gallate (EGCG), on wild-type human leiomyoma (WT-HuLM) cells and its potential action via catechol-o-methyltransferase (COMT) activity. Methods: Cell proliferation of WT-HuLM and COMT gene-silenced HuLM (COMT-shRNA-HuLM) cells treated with 0 or 100 µM EGCG for 7 days was measured using the MTT method. Total RNA and protein were extracted from cells treated with 0 or 100 µM of EGCG for 48 h. Gene expression profiling was performed using Human Signal Transduction PathwayFinder. Proliferation cell nuclear antigen (PCNA), cyclin-dependent kinase 4 (Cdk4) and COMT protein levels were detected by Western blot analyses. COMT enzyme activity was evaluated by HPLC. Results: EGCG-treated WT-HuLM cells showed significantly decreased COMT expression (p < 0.001) and enzyme activity (p < 0.05) compared to untreated WT-HuLM cells, while COMT-shRNA-HuLM cells showed no significant change. At 100 μM of EGCG, survival of WT-HuLM cells was significantly lower (p < 0.05) compared to COMT-shRNA-HuLM cells. EGCG treatment modulated multiple signaling pathways in WT-HuLM compared to untreated control, while changes were minimal or reversed in COMT-shRNA-HuLM cells. EGCG significantly decreased PCNA, Cdk4 and soluble COMT protein levels (p < 0.001) in WT-HuLM, but not in COMT-shRNA-HuLM cells. Conclusions: The antiproliferative and gene-modulating effects of EGCG on HuLM cells are mediated, at least partially, via its effect on COMT expression and enzyme activity.

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Protein Expression of Estrogen Receptors α and β and Aromatase in Myometrium and Uterine Leiomyoma

Cited by 32 publications

References 46 publications

Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

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

Green Tea Extract Inhibition of Human Leiomyoma Cell Proliferation Is Mediated via Catechol-<b><i>O</i></b>-Methyltransferase

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