Gland and epithelium formation in vitro from epithelial cells of the human endometrium

Negami, A. I.; Tominaga, Toshiro

doi:10.1093/oxfordjournals.humrep.a136954

Cited by 20 publications

(18 citation statements)

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“…Cyclopamine treatment suppressed the growth of NEG cells; however, there was no significant difference in the suppression caused by tomatidine. Thus, we consider that the cyclopamine-induced growth suppression may be due to a pharmacologic effect because the growth of cultured NEG cells has been reportedly more susceptible to various cell culture conditions compared with that of established carcinoma cell lines (29,30). In addition, Shh treatment did not significantly increase the growth of NEG cells, which may be explained by the lack of downstream effectors of this pathway.…”

Section: Discussionmentioning

confidence: 96%

Overexpression of Hedgehog Signaling Molecules and Its Involvement in the Proliferation of Endometrial Carcinoma Cells

Feng

Shiozawa²,

Miyamoto³

et al. 2007

Clinical Cancer Research

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Purpose: Research has revealed abnormal activation of the hedgehog pathway in human malignancies.The present study was undertaken to examine the expression and functional involvement of the hedgehog pathway in endometrial tissues. Experimental Design: The expression of sonic hedgehog (Shh), patched (Ptch), Smoothened (Smo), and Gli1was examined in various endometrial tissues and endometrial carcinoma cell lines. The effect of hedgehog signaling on the proliferation of endometrial carcinoma cell lines was also examined. Results: The expression of Shh, Ptch, Smo, and Gli1was very weak in normal endometrium, but was increased in endometrial hyperplasia and carcinoma stepwisely with significant differences. There was no marked difference in the expression of these molecules in carcinomas according to stages and histologic grades. Treatment with cyclopamine, a specific inhibitor of the hedgehog pathway, for endometrial carcinoma Ishikawa and HHUA cells suppressed growth by 56% and 67%, respectively, compared with the control. The addition of recombinant Shh peptide to HHUA cells enhanced their proliferation by 41%. The silencing of Gli1using small interfering RNA (siGli1) resulted in the growth suppression and down-regulation of Ptch expression. In addition, the cyclopamine/siGli1-induced growth suppression was associated with the down-regulation of cyclins D1 and A and N-myc. No somatic mutations for ptch and smo genes were detected in the endometrial carcinoma cases examined. Conclusions:The abnormal activation of this pathway is involved in the proliferation of endometrial carcinoma cells possibly in an auto-/paracrine fashion, suggesting the possibility of the hedgehog pathway being a novel candidate for molecular targeting.

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Section: Discussionmentioning

confidence: 96%

Overexpression of Hedgehog Signaling Molecules and Its Involvement in the Proliferation of Endometrial Carcinoma Cells

Feng

Shiozawa²,

Miyamoto³

et al. 2007

Clinical Cancer Research

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“…By contrast, established human endometrial carcinoma cell lines frequently employed in studies on EEC physiology have lost normal epithelial anchorage-dependent growth control (Isaka et al 2003). Cellular polarization is a critical parameter affecting numerous cell functions (Yeaman et al 1999) and has been shown in primary EECs to be important for embryo attachment and implantation (Meseguer et al 2001) and to enhance protein secretion (Negami & Tominaga 1989). hTERT-EECs cultured in a 3D collagen/fibroblast matrix displayed a polarized, non-invasive phenotype as illustrated by the production of a basal lamina and the formation of microvilli at the apical cell membrane.…”

Section: Discussionmentioning

confidence: 99%

“…Primary human EECs were reported to retain their polarization for a limited time period only (Classen-Linke et al 1997, Negami & Tominaga 1989 and, when grown on ECM material from an Engelbreth-Holm-Swarm tumor (MatrigelR), showed increased protein secretion (Negami & Tominaga 1989). This Matrigel, however, is supplemented with several growth factors including transforming growth factor-, EGF, insulin-like growth factor (IGF)-I, basic fibroblast growth factor and platelet-derived growth factor, and these growth factors and/or the tumor matrix itself may perturb physiological EEC responses.…”

Section: Steroid Hormone-responsive Htert-eecs · S Hombach-klonisch Amentioning

confidence: 99%

Regulation of functional steroid receptors and ligand-induced responses in telomerase-immortalized human endometrial epithelial cells

Hombach‐Klonisch¹,

Kehlen²,

Fowler³

et al. 2005

Journal of Molecular Endocrinology

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Information on the regulation of steroid hormone receptors and their distinct functions within the human endometrial epithelium is largely unavailable. We have immortalized human primary endometrial epithelial cells (EECs) isolated from a normal proliferative phase endometrium by stably transfecting the catalytic subunit (hTERT) of the human telomerase complex and cultured these hTERT-EECs now for over 350 population doublings. Active hTERT was detected in hTERT-EECs employing the telomerase repeat amplification assay protocol. hTERT-EECs revealed a polarized, non-invasive epithelial phenotype with apical microvilli and production of a basal lamina when grown on a three-dimensional collagen-fibroblast lattice. Employing atomic force microscopy, living hTERT-EECs were shown to produce extracellular matrix (ECM) components and ECM secretion was modified by estrogen and progesterone (P4). hTERT-EECs expressed inducible and functional endogenous estrogen receptor-alpha (ER-alpha) as demonstrated by estrogen response element reporter assays and induction of P4 receptor (PR). P4 treatment down-regulated PR expression, induced MUC-1 gene activity and resulted in increased ER-beta transcriptional activity. Gene activities of cytokines and their receptors interleukin (IL)-6, leukemia inhibitory factor (LIF), IL-11 and IL-6 receptor (IL6-R), LIF receptor and gp130 relevant to implantation revealed a 17 beta-estradiol (E2)-mediated up-regulation of IL-6 and an E2-and P4-mediated up-regulation of IL6-R in hTERT-EECs. Thus, hTERT-EECs may be regarded as a novel in vitro model to investigate the role of human EECs in steroid hormone-dependent normal physiology and pathologies, including implantation failure, endometriosis and endometrial cancer.

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“…Fractions [1][2][3][4] Samples of human endometrium were aseptically removed from the uterus obtained by hysterectomy performed for benign neo plasms. All patients consented to participate in this study.…”

Section: Preparation O F Human Endometrial Epithelial and Stromal Cellmentioning

confidence: 99%

“…A repair process of the endometrium, requiring epithelialization, takes place at the site of implantation, which mor phologically mimics endometrial regeneration following menstrual shedding. The fact that estradiol and progester one have no effect on epithelialization [1][2][3][4] has suggested the contribution of other factors in this process.We postulated the hypothesis that human hepatocyte growth factor (hHGF) is involved in the process of endo metrial regeneration. The growth factor is initially identi fied as a factor stimulating the growth of hepatocytes and later as a pleiotropic factor regulating the construction of the normal tissue architecture and acting as a mitogen, motogen and morphogen [5].…”

mentioning

confidence: 99%

Serum Human Hepatocyte Growth Factor in Human Menstrual Cycle and Pregnancy: A Novel Serum Marker of Regeneration and Reconstruction of Human Endometrium

et al. 1995

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Serum concentrations of human hepatocyte growth factor (hHGF) were measured in normal menstrual cycles and during uncomplicated pregnancies. In the normal menstrual cycle, the concentrations of hHGF increased through the mid and the late luteal phases to reach the highest peak during the menstrual phases, followed by a gradual decline during the follicular phase toward the trough levels seen in the ovulatory and the very early luteal phases. During pregnancy, serum hHGF concentrations increased continuously from the late luteal levels and constituted 4 distinct peaks. By immunostaining, c-Met protein, a receptor for hHGF, was localized not in the stromal but in the epithelial layer of the endometrium. In cultured isolated endometrial cells, hHGF stimulated the proliferation of both the epithelial and the stromal cells. It is likely that hHGF is involved in the repair or reconstruction process of the endometrium after menstrual shedding and implantation.

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Gland and epithelium formation in vitro from epithelial cells of the human endometrium

Cited by 20 publications

References 0 publications

Overexpression of Hedgehog Signaling Molecules and Its Involvement in the Proliferation of Endometrial Carcinoma Cells

Overexpression of Hedgehog Signaling Molecules and Its Involvement in the Proliferation of Endometrial Carcinoma Cells

Regulation of functional steroid receptors and ligand-induced responses in telomerase-immortalized human endometrial epithelial cells

Serum Human Hepatocyte Growth Factor in Human Menstrual Cycle and Pregnancy: A Novel Serum Marker of Regeneration and Reconstruction of Human Endometrium

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