Expression of Sonic hedgehog signaling molecules in normal, hyperplastic and carcinomatous endometrium

Kim, Kyung Hee; Kim, Jin Man; Choi, Yoon–La; Shin, Young Kee; Lee, Ho-chang; Seong, In Ock; Kim, Bum Kyung; Chae, Seoung Wan; Chung, Yun-Shin; Kim, Seok-Hyung

doi:10.1111/j.1440-1827.2009.02366.x

Cited by 27 publications

(21 citation statements)

References 22 publications

(46 reference statements)

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“…A fibroid-associated increase in CTNNB1 confirms microarray data by us and others (Luo et al 2005a, Zaitseva et al 2006. Aberrant expression/ mutations of CTNNB1 leading to increased nuclear localisation, and enhanced Wnt signalling, have been observed in endometrial carcinoma (Fukuchi et al 1998, Saegusa & Okayasu 2001, Moreno-Bueno et al 2002, Kim et al 2009). Non-uterine smooth muscle tumours similarly demonstrate increased CTNNB1 expression and nuclear translocation during proliferation or predisposing tumour development (Gosens et al 2010, van Veelen et al 2011).…”

Section: Nr2f2 and Ctnnb1 In Uterine Fibroidssupporting

confidence: 70%

“…Acting through its receptor (PR), progesterone increases uterine expression of HH protein, which in turn regulates NR2F2 expression (Lee et al 2006b, Simon et al 2009a. HH is crucial to normal and abnormal uterine (and endometrial) development and is also regulated by progesterone (Feng et al 2007, Kim et al 2009, Wei et al 2010, Franco & Yao 2012. Currently, however, data are lacking on the potential roles of progesterone, RA and/or SHH regulatory molecules in controlling CTNNB1 and/or NR2F2 in human myometrium and fibroid tissues.…”

Section: Introductionmentioning

confidence: 99%

“…The HH pathway is important in many normal and abnormal cellular functions, including embryonic development, stem cell proliferation and cancer genesis (reviewed by Varjosalo & Taipale (2008), Choi et al (2011), Harris et al (2011) and Park et al (2011)). The HH pathway is also crucial to the development of reproductive tract (Franco & Yao 2012), uterine function (Takamoto et al 2005, Lee et al 2006a) and uterine malignancies (Feng et al 2007, Kim et al 2009). Despite evidence for a role of HH in the uterus, and our results demonstrate that the HH pathway is active in cultured myometrial and fibroid cells; NR2F2 and CTNNB1 mRNA expressions were not affected by SHH treatment.…”

Section: Nr2f2 and Ctnnb1 In Uterine Fibroidsmentioning

confidence: 99%

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Aberrant expression and regulation of NR2F2 and CTNNB1 in uterine fibroids

Zaitseva¹,

Holdsworth-Carson²,

Waldrip³

et al. 2013

Reproduction

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Uterine fibroids are the most common benign tumour afflicting women of reproductive age. Despite the large healthcare burden caused by fibroids, there is only limited understanding of the molecular mechanisms that drive fibroid pathophysiology. Although a large number of genes are differentially expressed in fibroids compared with myometrium, it is likely that most of these differences are a consequence of the fibroid presence and are not causal. The aim of this study was to investigate the expression and regulation of NR2F2 and CTNNB1 based on their potential causal role in uterine fibroid pathophysiology. We used real-time quantitative RT-PCR, western blotting and immunohistochemistry to describe the expression of NR2F2 and CTNNB1 in matched human uterine fibroid and myometrial tissues. Primary myometrial and fibroid smooth muscle cell cultures were treated with progesterone and/or retinoic acid (RA) and sonic hedgehog (SHH) conditioned media to investigate regulatory pathways for these proteins. We showed that NR2F2 and CTNNB1 are aberrantly expressed in fibroid tissue compared with matched myometrium, with strong blood vessel-specific localisation. Although the SHH pathway was shown to be active in myometrial and fibroid primary cultures, it did not regulate NR2F2 or CTNNB1 mRNA expression. However, progesterone and RA combined regulated NR2F2 mRNA, but not CTNNB1, in myometrial but not fibroid primary cultures.In conclusion, we demonstrate aberrant expression and regulation of NR2F2 and CTNNB1 in uterine fibroids compared with normal myometrium, consistent with the hypothesis that these factors may play a causal role uterine fibroid development.

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Section: Nr2f2 and Ctnnb1 In Uterine Fibroidssupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Section: Nr2f2 and Ctnnb1 In Uterine Fibroidsmentioning

confidence: 99%

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Aberrant expression and regulation of NR2F2 and CTNNB1 in uterine fibroids

Zaitseva¹,

Holdsworth-Carson²,

Waldrip³

et al. 2013

Reproduction

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“…Further, treatment of Ishikawa and HHUA cells with cyclopamine, a specific inhibitor of Hh pathway suppressed growth of these cell lines by 56 and 67% respectively. Later, Kim et al (2009) reported an overall increase in expression of Hh signaling molecules in hyperplastic endometrium as compared to normal endometrium. In carcinoma samples extensive alterations in the expression pattern of signaling molecules were observed.…”

Section: Cell Signaling Pathwaysmentioning

confidence: 99%

Tumor progression, metastasis, and modulators of epithelial–mesenchymal transition in endometrioid endometrial carcinoma: an update

Makker

Goel

2015

Endocrine-Related Cancer

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Endometrioid endometrial carcinoma (EEC), also known as type 1 endometrial cancer (EC), accounts for over 70-80% of all cases that are usually associated with estrogen stimulation and often develops in a background of atypical endometrial hyperplasia. The increased incidence of EC is mainly confined to this type of cancer. Most EEC patients present at an early stage and generally have a favorable prognosis; however, up to 30% of EEC present as high risk tumors, which have invaded deep into the myometrium at diagnosis and progressively lead to local or extra pelvic metastasis. The poor survival of advanced EC is related to the lack of effective therapies, which can be attributed to poor understanding of the molecular mechanisms underlying the progression of disease toward invasion and metastasis. Multiple lines of evidence illustrate that epithelial-mesenchymal transition (EMT)-like events are central to tumor progression and malignant transformation, endowing the incipient cancer cell with invasive and metastatic properties. The aim of this review is to summarize the current knowledge on molecular events associated with EMT in progression, invasion, and metastasis of EEC. Further, the role of epigenetic modifications and microRNA regulation, tumor microenvironment, and microcystic elongated and fragmented glands like invasion pattern have been discussed. We believe this article may perhaps stimulate further research in this field that may aid in identifying high risk patients within this clinically challenging patient group and also lead to the recognition of novel targets for the prevention of metastasis -the most fatal consequence of endometrial carcinogenesis.

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“…1; table 1). Kim et al [15] described that the marked reduction in the molecule in atrophic endometrium had functional significance in the menstrual cycle, suggesting the functional significance of the Notch signaling pathway. It has been reported that the Notch signaling pathway regulates cellular proliferation in various cell types [9,10,11], and our study confirmed that the LI of Notch-1 in proliferative endometrium was significantly higher than those at other phases (table 1).…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Utility of Notch-1 Immunocytochemistry in Endometrial Cytology

Mori¹,

Miyamoto

Ohno

et al. 2012

Acta Cytologica

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Objective: It was the aim of this study to evaluate the diagnostic utility of Notch-1 immunocytochemistry in distinguishing endometrial glandular and stromal breakdown (EGBD) from endometrial adenocarcinoma in endometrial cytology. Study Design: Samples of normal endometrium, EGBD and endometrial adenocarcinoma were subjected to immunocytochemical staining for Notch-1, and we examined the labeling index (LI) of Notch-1 (the ratio of intranuclear Notch-1-positive cells to total cells). We compared (1) the Notch-1 LI in normal endometrium, (2) the Notch-1 LI between normal endometrium and endometrial adenocarcinoma, and (3) the Notch-1 LI in normal endometrium, EGBD and endometrial adenocarcinoma. Results: In analysis item 1, the LI of Notch-1 was 32.9 ± 8.4, 19.4 ± 8.2 and 12.5 ± 7.5% in proliferative endometrium, secretory endometrium and atrophic endometrium, respectively. In analysis item 2, the LI of Notch-1 in endometrial adenocarcinoma was 45.2 ± 7.4%, which was significantly higher than that in normal endometrium. In analysis item 3, the LI of Notch-1 in EGBD was 31.3 ± 8.3%, which was significantly lower than that in endometrial adenocarcinoma. Conclusion: In conclusion, Notch-1 immunocytochemistry is a useful method for distinguishing between EGBD and endometrial carcinoma in endometrial cytology.

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Expression of Sonic hedgehog signaling molecules in normal, hyperplastic and carcinomatous endometrium

Cited by 27 publications

References 22 publications

Aberrant expression and regulation of NR2F2 and CTNNB1 in uterine fibroids

Aberrant expression and regulation of NR2F2 and CTNNB1 in uterine fibroids

Tumor progression, metastasis, and modulators of epithelial–mesenchymal transition in endometrioid endometrial carcinoma: an update

Diagnostic Utility of Notch-1 Immunocytochemistry in Endometrial Cytology

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