Phenotypic plasticity of the ovarian surface epithelium: TGF-beta 1 induction of epithelial to mesenchymal transition (EMT) in vitro.

Abstract:

:Ovarian surface epithelium (OSE) is the most conceivable cell origin of epithelial ovarian carcinomas. Unlike many other epithelial tumors, the precancerous lesion acquires expression of epithelial markers, e.g. E-cadherin and claudins, suggesting that OSE cells undergo mesenchymal to epithelial transition (MET) during transformation. Recent findings indicate that TGF-β1, a prototypic stimulus of epithelial to mesenchymal transition (EMT), i.e. reverse to MET, is produced at significant amounts in the intact ovary. In the present study, we therefore investigated whether TGF-β1 changes the OSE phenotype accordingly, focusing on epithelial junction proteins and transcriptional EMT regulators quantified by real-time RT-PCR and Western blotting in cultured normal human OSE. Early OSE passages were found to paradoxically express de novo E-cadherin and also establish tight junctions exhibiting claudin-1 (but not claudin-3 and -4) and occludin. Stimulation with TGF-β1 (100 ng/ml) for 3-5 d down-regulated all these epithelial markers including Crumbs3 and also prevented the formation of an epithelial barrier This was accompanied by sustained expression of Snail and N-cadherin and transient expression of Slug, whereas Zeb1 (zinc finger E-box binding homeobox 1) and Twist mRNA levels were not significantly changed. In conclusion, TGF-β1 enforces the mesenchymal phenotype of OSE cells in vitro by an EMT-like process, leading to an altered molecular composition of the epithelial junction complex that partly coincides with the expression pattern of the native OSE. This suggests a potential role of TGF-β1-induced EMT in OSE under physiological conditions and possibly also in epithelial ovarian tumorigenesis.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Zhu Y,Nilsson M,Sundfeldt K

doi

10.1210/en.2010-0486

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

5497-505

issue

11

eissn

0013-7227

issn

1945-7170

pii

en.2010-0486

journal_volume

151

pub_type

杂志文章
  • Induction of somatogenic receptors in livers of hypersomatotropic rats.

    abstract::Male and female Wistar-Furth rats bearing the pituitary tumor MtT/W15 had serum GH and PRL levels several hundred-fold higher, and immunoreactive somatomedin levels 3-fold higher, than those of controls. The presence of tumor appeared to have no effect on specific binding of radioiodinated bovine GH to liver microsoma...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-111-3-1020

    authors: Baxter RC,Zaltsman Z,Turtle JR

    更新日期:1982-09-01 00:00:00

  • Neuromedin-N is not released with neurotensin from rat ileum.

    abstract::Neuromedin-N (NN) and neurotensin (NT) were shown recently to be encoded in the same precursor molecule. Colocalization and corelease of ileal NT and NN have not yet been demonstrated and were investigated in the rat using antisera that separately recognized intact NT and NN in ileal extracts. Immunofluorescence label...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-126-3-1584

    authors: Cuber JC,Herrmann C,Kitabgi P,Bosshard A,Bernard C,De Nadai F,Chayvialle JA

    更新日期:1990-03-01 00:00:00

  • 11β-HSD1 Modulates the Set Point of Brown Adipose Tissue Response to Glucocorticoids in Male Mice.

    abstract::Glucocorticoids (GCs) are potent regulators of energy metabolism. Chronic GC exposure suppresses brown adipose tissue (BAT) thermogenic capacity in mice, with evidence for a similar effect in humans. Intracellular GC levels are regulated by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity, which can amplify...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2016-1722

    authors: Doig CL,Fletcher RS,Morgan SA,McCabe EL,Larner DP,Tomlinson JW,Stewart PM,Philp A,Lavery GG

    更新日期:2017-06-01 00:00:00

  • Arginine vasopressin triggers intracellular calcium release, a calcium-activated potassium current and exocytosis in identified rat corticotropes.

    abstract::Arginine vasopressin (AVP) stimulates the secretion of ACTH from pituitary corticotropes. We investigated the action of AVP in single corticotropes of male rats. Corticotropes were identified with the reverse hemolytic plaque assay using antibodies against ACTH. Using the whole-cell recording technique in conjunction ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.139.5.5999

    authors: Tse A,Lee AK

    更新日期:1998-05-01 00:00:00

  • Inhibition of transcription affects synthesis of steroidogenic acute regulatory protein and steroidogenesis in MA-10 mouse Leydig tumor cells.

    abstract::Hormonal induction of steroidogenesis in the adrenal and gonads is dependent on the synthesis and function of the steroidogenic acute regulatory protein (StAR). As a first approach to investigate the role of translation in the control of StAR expression, we examined StAR protein synthesis and steroid production in MA-...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.138.11.5535

    authors: Clark BJ,Combs R,Hales KH,Hales DB,Stocco DM

    更新日期:1997-11-01 00:00:00

  • Expression of messenger ribonucleic acid encoding tissue inhibitor of metalloproteinases-2 within ovine follicles and corpora lutea.

    abstract::Metalloproteinase inhibitors, such as tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and -2), play a key role in the regulation of metalloproteinases that modify extracellular matrix composition. Although expression of TIMP-1 within ovarian tissues has been well characterized, little information is available ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.136.2.7835290

    authors: Smith GW,McCrone S,Petersen SL,Smith MF

    更新日期:1995-02-01 00:00:00

  • Up-regulating relaxin expression by G-quadruplex interactive ligand to achieve antifibrotic action.

    abstract::Myocardial fibrosis is a key pathological change in a variety of heart diseases contributing to the development of heart failure, arrhythmias, and sudden death. Recent studies have shown that relaxin prevents and reverses cardiac fibrosis. Endogenous expression of relaxin was elevated in the setting of heart disease; ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2012-1114

    authors: Gu HP,Lin S,Xu M,Yu HY,Du XJ,Zhang YY,Yuan G,Gao W

    更新日期:2012-08-01 00:00:00

  • Atypical synergistic alpha 1- and beta-adrenergic regulation of adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate in rat pinealocytes.

    abstract::The adrenergic control of cAMP and 3',5'-cyclic GMP (cGMP) in dispersed adult rat pinealocytes was investigated. Norepinephrine treatment increased cAMP and cGMP content 60- and 400-fold, respectively; both alpha- and beta-adrenoceptors had to be activated for these responses to occur. Beta-Adrenergic stimulation alon...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-116-6-2167

    authors: Vanecek J,Sugden D,Weller J,Klein DC

    更新日期:1985-06-01 00:00:00

  • Gonadotropin-releasing hormone (GnRH) activates the m-current in GnRH neurons: an autoregulatory negative feedback mechanism?

    abstract::GnRH autoregulates GnRH neurons through an ultrashort feedback loop. One potential mechanism is the regulation of K(+) channel activity through the GnRH receptor. Whereas GnRH inhibits the activity of the M-current in peripheral neurons, there is no direct evidence that the M-current is involved in the autoregulatory ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2007-1178

    authors: Xu C,Roepke TA,Zhang C,Rønnekleiv OK,Kelly MJ

    更新日期:2008-05-01 00:00:00

  • Insulin-like growth factor I increases rat peptide YY promoter activity through Sp1 binding sites.

    abstract::Studies in rodents demonstrate that the mitogen, IGF-I, stimulates intestinal peptide YY (PYY) expression. To investigate whether the stimulatory influence of IGF-I is exerted at the level of gene transcription, rat PYY 5'-upstream sequences (-2800/+37 bp, -770/+37 bp, -127/+37 bp) fused to the firefly luciferase (luc...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2003-0770

    authors: Wang G,Leiter AB,Englander EW,Greeley GH Jr

    更新日期:2004-02-01 00:00:00

  • Nerve growth factor enhances [3H]nicotine binding to a nicotinic cholinergic receptor on PC 12 cells.

    abstract::Although nicotinic cholinergic agonists have functional effects on PC 12 cells, radioligand-binding sites have not been detected. We, therefore, studied PC 12 cells incubated in the presence of nerve growth factor (NGF) and determined that specific [3H]nicotine-binding sites were induced approximately 2.5-fold in the ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.130.2.1733730

    authors: Madhok TC,Sharp BM

    更新日期:1992-02-01 00:00:00

  • Mothers against decapentaplegic-related protein 2 expression in avian granulosa cells is up-regulated by transforming growth factor beta during ovarian follicular development.

    abstract::Although mothers against dpp (MAD) and its related proteins (MADR) are believed to be important components of the cell signaling pathway for the transforming growth factor beta (TGFbeta) superfamily, the presence and regulation of these signaling molecules in ovarian cells by TGFbeta is not known. In the present studi...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.138.9.5376

    authors: Li M,Li J,Hoodless PA,Tzukazaki T,Wrana JL,Attisano L,Tsang BK

    更新日期:1997-09-01 00:00:00

  • Cholera toxin and dibutyryl cyclic adenosine 3',5'-monophosphate sensitize gonadotropin-releasing hormone-stimulated inositol phosphate production to inhibition in protein kinase-C (PKC)-depleted cells: evidence for cross-talk between a cholera toxin-sens

    abstract::The present study assesses the relationship between G-proteins and protein kinase-C (PKC) in the gonadotrope. Cells were depleted of PKC with 1 microM phorbol 12-myristate 13-acetate for 12 h, followed by medium 199-BSA for 6 h before treatment with vehicle, pertussis toxin (PTX), cholera toxin (CTX), or (Bu)2cAMP (dB...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.133.6.8243300

    authors: Barnes SJ,Conn PM

    更新日期:1993-12-01 00:00:00

  • Antagonistic roles of Dmrt1 and Foxl2 in sex differentiation via estrogen production in tilapia as demonstrated by TALENs.

    abstract::Transcription activator-like effector nucleases (TALENs) are a powerful approach for targeted genome editing and have been proved to be effective in several organisms. In this study, we reported that TALENs can induce somatic mutations in Nile tilapia, an important species for worldwide aquaculture, with reliably high...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2013-1451

    authors: Li MH,Yang HH,Li MR,Sun YL,Jiang XL,Xie QP,Wang TR,Shi HJ,Sun LN,Zhou LY,Wang DS

    更新日期:2013-12-01 00:00:00

  • In situ hybridization detection of marked differences in pre-proopiomelanocortin messenger ribonucleic acid content of individual corticotropes and melanotropes.

    abstract::Recently, heterogeneity of POMC mRNA content between intermediate lobe melanotropes of the rat pituitary gland was demonstrated by in situ hybridization of tissue sections. In the present study the heterogeneity of POMC mRNA content in dispersed rat pituitary cells has been investigated. Acutely dispersed cells from a...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-124-3-1359

    authors: Hatfield JM,Daikh DI,Adelman JP,Douglass J,Bond CT,Allen RG

    更新日期:1989-03-01 00:00:00

  • Identification of signal transduction pathways that modulate dibutyryl cyclic adenosine monophosphate activation of stanniocalcin gene expression in neuroblastoma cells.

    abstract::Stanniocalcin (STC) is a new mammalian polypeptide hormone and appears to be a regulator of neuronal function. We have already shown that the induction of STC mRNA and protein expression by cAMP is integral to neuroblastoma cell differentiation, particularly neurite outgrowth. In this study, we examined the cAMP pathw...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2003-0504

    authors: Yeung HY,Chan DK,Mak NK,Wagner GF,Wong CK

    更新日期:2003-10-01 00:00:00

  • Implication of the Tpl2 kinase in inflammatory changes and insulin resistance induced by the interaction between adipocytes and macrophages.

    abstract::Adipose tissue inflammation is associated with the development of insulin resistance. In obese adipose tissue, lipopolysaccharides (LPSs) and saturated fatty acids trigger inflammatory factors that mediate a paracrine loop between adipocytes and macrophages. However, the inflammatory signaling proteins underlying this...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2013-1815

    authors: Ceppo F,Berthou F,Jager J,Dumas K,Cormont M,Tanti JF

    更新日期:2014-03-01 00:00:00

  • Long term inhibitory effects of pancreastatin and diazepam binding inhibitor on pancreatic beta-cell deoxyribonucleic acid replication, polyamine content, and insulin secretion.

    abstract::The two peptides pancreastatin and diazepam binding inhibitor (DBI) were recently demonstrated in pancreatic islets and were shown to inhibit insulin secretion in short term experiments. In the present study we investigated long term effects of pancreastatin and DBI on the DNA synthesis, polyamine content, and insulin...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-128-6-3277

    authors: Sjöholm A,Funakoshi A,Efendić S,Ostenson CG,Hellerström C

    更新日期:1991-06-01 00:00:00

  • Characterization of the synthesis and secretion of transforming growth factor-alpha from salivary glands and saliva.

    abstract::Whole saliva collected from rat, mouse, and human sources was found to contain high concentrations of transforming growth factor-alpha (TGF alpha) when analyzed by RIA. The concentrations of TGF alpha in unstimulated human saliva (age, 30-45 yr; n = 10; 1.5 +/- 3.1 nM) was reduced with age (age, 55-70 yr; n = 10; 0.4 ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.134.2.8299590

    authors: Humphreys-Beher MG,Macauley SP,Chegini N,van Setten G,Purushotham K,Stewart C,Wheeler TT,Schultz GS

    更新日期:1994-02-01 00:00:00

  • The actions of tuberoinfundibular peptide on the hypothalamo-pituitary axes.

    abstract::Tuberoinfundibular peptide is a recently discovered agonist for the PTH receptor-2; the latter has a wide distribution including the external zone of the median eminence of the hypothalamus, suggesting a role in neuroendocrine function. We have investigated the effects of tuberoinfundibular peptide on the hypothalamo-...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.142.8.8308

    authors: Ward HL,Small CJ,Murphy KG,Kennedy AR,Ghatei MA,Bloom SR

    更新日期:2001-08-01 00:00:00

  • Developmental exposure to Bisphenol a impairs the uterine response to ovarian steroids in the adult.

    abstract::Morphoregulator genes like members of the Hox gene family regulate uterine development and are associated with endocrine-related processes such as endometrial proliferation and differentiation in the adult uterus. Exposure to neonatal endocrine disruptors could affect signaling events governed by Hox genes, altering t...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2008-0651

    authors: Varayoud J,Ramos JG,Bosquiazzo VL,Muñoz-de-Toro M,Luque EH

    更新日期:2008-11-01 00:00:00

  • Mice lacking the calcineurin inhibitor Rcan2 have an isolated defect of osteoblast function.

    abstract::Calcineurin-nuclear factor of activated T cells signaling controls the differentiation and function of osteoclasts and osteoblasts, and regulator of calcineurin-2 (Rcan2) is a physiological inhibitor of this pathway. Rcan2 expression is regulated by T(3), which also has a central role in skeletal development and bone ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2011-1814

    authors: Bassett JH,Logan JG,Boyde A,Cheung MS,Evans H,Croucher P,Sun XY,Xu S,Murata Y,Williams GR

    更新日期:2012-07-01 00:00:00

  • Delayed puberty in spontaneously hypertensive rats involves a primary ovarian failure independent of the hypothalamic KiSS-1/GPR54/GnRH system.

    abstract::Spontaneously hypertensive (SH) rats, extensively used as experimental models of essential human hypertension, display important alterations in the neuroendocrine reproductive axis, which manifest as markedly delayed puberty onset in females but whose basis remains largely unknown. We analyze herein in female SH rats:...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2008-1381

    authors: Pinilla L,Castellano JM,Romero M,Tena-Sempere M,Gaytán F,Aguilar E

    更新日期:2009-06-01 00:00:00

  • Evidence that adenosine 3',5'-monophosphate mediates hormonal stimulation of prostaglandin production in cultured mouse parietal bones.

    abstract::The present investigation was undertaken to examine the possible role of cAMP in PTH-stimulated prostaglandin (PG) production in organ cultures of neonatal mouse parietal bones. Cultures were treated with PTH, forskolin, isobutylmethylxanthine (IBMX), and 8-bromo-cAMP (8BrcAMP). We found that similar concentrations of...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-126-2-1070

    authors: Klein-Nulend J,Bowers PN,Raisz LG

    更新日期:1990-02-01 00:00:00

  • Attenuation by a 5 alpha-reductase inhibitor of the activational effect of testosterone propionate on penile erections in castrated male rats.

    abstract::Daily administration of an inhibitor of 5 alpha-reductase, 17 beta-testosterone carboxylic acid, significantly attenuated the stimulatory effect of testosterone propionate on penile erections displayed by castrated male rats which were restrained in a supine position. This treatment, however, failed to affect mating b...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-109-4-1047

    authors: Bradshaw WG,Baum MJ,Awh CC

    更新日期:1981-10-01 00:00:00

  • Regulation of low molecular weight insulin-like growth factor binding proteins in experimental diabetes mellitus.

    abstract::Circulating insulin-like growth factor (IGF) bioactivity is reduced in animals and patients with diabetes mellitus. We sought to determine whether the availability and levels of specific IGF binding proteins (BPs) are altered in animals with experimental diabetes, and might contribute to changes in circulating IGF bio...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-126-5-2614

    authors: Unterman TG,Patel K,Mahathre VK,Rajamohan G,Oehler DT,Becker RE

    更新日期:1990-05-01 00:00:00

  • The mechanisms underlying the glucose dependence of arginine vasopressin-induced insulin secretion in beta-cells.

    abstract::The mechanisms underlying the glucose dependence of arginine vasopressin (AVP)-stimulated insulin secretion were examined in a hamster insulin-secreting cell line (HIT cells). At 1.67 mM glucose, 100 nM AVP stimulated biphasic changes in free cytosolic Ca2+ ([Ca2+]i) and insulin secretion. The initial spike of [Ca2+]i...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.132.5.8386610

    authors: Lu M,Soltoff SP,Yaney GC,Boyd AE 3rd

    更新日期:1993-05-01 00:00:00

  • Studies of melatonin effects on epithelia using the human embryonic kidney-293 (HEK-293) cell line.

    abstract::The expression of melatonin receptors (MR) of the Mel1a subtype in basolateral membrane of guinea pig kidney proximal tubule suggests that melatonin plays a role in regulating epithelial functions. To investigate the cellular basis of melatonin action on epithelia, we sought to establish an appropriate in vitro cultur...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.138.11.5524

    authors: Chan CW,Song Y,Ailenberg M,Wheeler M,Pang SF,Brown GM,Silverman M

    更新日期:1997-11-01 00:00:00

  • Carboxypeptidase H processing and secretion in rat clonal beta-cell lines.

    abstract::Carboxypeptidase H (CP-H, EC 3.4.17.10) removes C-terminal basic amino acids from insulin and many other peptide hormone intermediates in endocrine and neural tissues. CP-H was studied in two rat insulinoma-derived clonal beta-cell lines that were chosen in part because their profile of hormone production is restricte...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.131.3.1505450

    authors: Fiedorek FT Jr,Parkinson D

    更新日期:1992-09-01 00:00:00

  • Vascular endothelial growth factor receptor 2 (VEGFR-2) functions to promote uterine decidual angiogenesis during early pregnancy in the mouse.

    abstract::Implantation of an embryo induces rapid proliferation and differentiation of uterine stromal cells, forming a new structure, the decidua. One salient feature of decidua formation is a marked increase in maternal angiogenesis. Vascular endothelial growth factor (VEGF)-dependent pathways are active in the ovary, uterus,...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2008-1207

    authors: Douglas NC,Tang H,Gomez R,Pytowski B,Hicklin DJ,Sauer CM,Kitajewski J,Sauer MV,Zimmermann RC

    更新日期:2009-08-01 00:00:00