We report that decreased expression of miR-30c in tumor compared to adjacent tissue is sex-dependent in colorectal cancer (CRC) patients. High expression of miR-30c was associated with better survival in the whole cohort. When the cohort was split into male and female subcohorts, decreased miR-30c expression in tumor compared to adjacent tissue was observed only in males. Expression of miR-30c was decreased in CRC tumor tissue in male patients with nodes involvement compared to those without metastases in nodes and this difference was not observe in females. Next dependency of miR-30c expression on oestrogen receptor beta (ERbeta) mRNA levels in tumor was tested. In males with low expression of ERbeta, we observed a significant decrease in miR-30c levels in patients with nodes involvement compared to those without nodes involvement. This difference was not observed in males with high ERbeta mRNA levels and in females. Accordingly, males with low expression of ERbeta and high expression of miR-30c showed a better survival that those with low expression ERbeta and low expression of miR-30c. It is possible to conclude that whole cohort survival dependence on miR-30c is mostly generated by a subcohort of males with low expression of ERbeta mRNA in tumor tissue.

• MeSH
• beta receptor estrogenů genetika   metabolismus   MeSH
• kohortové studie MeSH
• kolorektální nádory genetika   metabolismus   patologie   MeSH
• lidé MeSH
• mikro RNA biosyntéza   genetika   MeSH
• míra přežití MeSH
• nádorové biomarkery biosyntéza   genetika   MeSH
• prognóza MeSH
• senioři MeSH
• sexuální faktory MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The incidence of colorectal cancer (CRC) shows a sex-dependent difference in humans. The aim of this study was to analyze estrogen receptor beta mRNA (ERbeta) expression in patients with CRC with respect to their gender and clinicopathological features. Since cancer progression is accompanied by tumor vascularization, VEGF-A (vascular endothelial growth factor A) transcription was analyzed along with ERbeta mRNA. ERbeta mRNA was also correlated with the expression of clock genes, which are known to influence the cell cycle. ERbeta mRNA expression in females with CRC showed an inverse association with increasing tumor staging that was not observed in males. Lower levels of ERbeta mRNA were observed in females with a higher clinical stage compared with those with earlier-stage tumors. ERbeta mRNA expression showed a significant positive correlation with mRNA of clock genes period 2 and cryptochrome 2 in healthy but not in cancerous tissue in males. Expression of VEGF-A mRNA showed a negative correlation with ERbeta mRNA after splitting of the cohort according to gender and nodus involvement. We propose that gender differences in ERbeta mRNA expression in tumors during the early stages of CRC can partially explain the lower occurrence of CRC in females compared with males.

• MeSH
• beta receptor estrogenů metabolismus   MeSH
• cirkadiánní rytmus - signální peptidy a proteiny metabolismus   MeSH
• kohortové studie MeSH
• kolorektální nádory metabolismus   MeSH
• lidé MeSH
• pohlavní dimorfismus * MeSH
• senioři MeSH
• vaskulární endoteliální růstový faktor A metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Estrogen deprivation is considered responsible for many age-related processes, including poor wound healing. Guided by previous observations that estradiol accelerates re‑epithelialization through estrogen receptor (ER)‑β, in the present study, we examined whether selective ER agonists [4,4',4''-(4-propyl [1H] pyrazole-1,3,5-triyl)‑trisphenol (PPT), ER‑α agonist; 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN), ER‑β agonist] affect the expression of basic proliferation and differentiation markers (Ki‑67, keratin‑10, ‑14 and ‑19, galectin‑1 and Sox‑2) of keratinocytes using HaCaT cells. In parallel, ovariectomized rats were treated daily with an ER modulator, and wound tissue was removed 21 days after wounding and routinely processed for basic histological analysis. Our results revealed that the HaCaT keratinocytes expressed both ER‑α and ‑β, and thus are well-suited for studying the effects of ER agonists on epidermal regeneration. The activation of ER‑α produced a protein expression pattern similar to that observed in the control culture, with a moderate expression of Ki‑67 being observed. However, the activation of ER‑β led to an increase in cell proliferation and keratin‑19 expression, as well as a decrease in galectin‑1 expression. Fittingly, in rat wounds treated with the ER‑β agonist (DPN), epidermal regeneration was accelerated. In the present study, we provide information on the mechanisms through which estrogens affect the expression patterns of selected markers, thus modulating keratinocyte proliferation and differentiation; in addition, we demonstrate that the pharmacological activation of ER-α and -β has a direct impact on wound healing.

• MeSH
• alfa receptor estrogenů agonisté   metabolismus   MeSH
• beta receptor estrogenů agonisté   metabolismus   MeSH
• buněčná diferenciace účinky léků   MeSH
• buněčné linie MeSH
• fenoly farmakologie   MeSH
• hojení ran účinky léků   MeSH
• keratinocyty cytologie   účinky léků   metabolismus   patologie   MeSH
• kůže účinky léků   metabolismus   patologie   MeSH
• lidé MeSH
• nitrily farmakologie   MeSH
• potkani Sprague-Dawley MeSH
• pyrazoly farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Wedelolactone, a plant coumestan, was shown to act as anti-cancer agent for breast and prostate carcinomas in vitro and in vivo targeting multiple cellular proteins including androgen receptors, 5-lipoxygenase and topoisomerase IIα. It is cytotoxic to breast, prostate, pituitary and myeloma cancer cell lines in vitro at μM concentrations. In this study, however, a novel biological activity of nM dose of wedelolactone was demonstrated. Wedelolactone acts as agonist of estrogen receptors (ER) α and β as demonstrated by transactivation of estrogen response element (ERE) in cells transiently expressing either ERα or ERβ and by molecular docking of this coumestan into ligand binding pocket of both ERα and ERβ. In breast cancer cells, wedelolactone stimulates growth of estrogen receptor-positive cells, expression of estrogen-responsive genes and activates rapid non-genomic estrogen signalling. All these effects can be inhibited by pretreatment with pure ER antagonist ICI 182,780 and they are not observed in ER-negative breast cancer cells. We conclude that wedelolactone acts as phytoestrogen in breast cancer cells by stimulating ER genomic and non-genomic signalling pathways.

• MeSH
• aktivace transkripce genetika   MeSH
• alfa receptor estrogenů metabolismus   MeSH
• antagonisté estrogenového receptoru farmakologie   MeSH
• beta receptor estrogenů metabolismus   MeSH
• estradiol analogy a deriváty   farmakologie   MeSH
• estrogeny farmakologie   MeSH
• HEK293 buňky MeSH
• kumariny farmakologie   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• nádorové buněčné linie MeSH
• nádory prsu farmakoterapie   MeSH
• proliferace buněk účinky léků   MeSH
• protinádorové látky farmakologie   MeSH
• responzivní elementy genetika   MeSH
• signální transdukce účinky léků   MeSH
• simulace molekulového dockingu MeSH
• transkripční faktor AP-1 metabolismus   MeSH
• vazebná místa účinky léků   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• alfa receptor estrogenů metabolismus   MeSH
• beta receptor estrogenů metabolismus   MeSH
• endometrióza metabolismus   patofyziologie   MeSH
• endometrium fyziologie   metabolismus   patologie   MeSH
• lidé MeSH
• receptory pro estrogeny metabolismus   MeSH
• receptory spřažené s G-proteiny metabolismus   MeSH
• transkripční faktory MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH

Antiangiogenic activity of the brassinosteroid plant hormones (BRs) and their derivative cholestanon was investigated in human umbilical vein endothelial cells (HUVEC) and in human microvascular endothelial cells (HMEC-1). 24-Epibrassinolide and 28-homocastasterone from group of 21 tested natural BRs inhibited migration of HUVEC cells. Seven tested BRs decreased the number of tubes significantly. Synthetic analogue cholestanon inhibited angiogenesis in vitro more effectively than natural BRs. Because of the similarity of BRs to human steroids, we have also studied interactions of BRs with human steroid receptors. Synthetic BRs cholestanon showed agonistic effects on estrogen-receptor-α, estrogen-receptor-β and androgen receptor. Of the natural BRs, 24-epibrassinolide was found to be a weak antagonist of estrogen-receptor-α (ERα). Our results provide the first evidence that large group of BRs can inhibit in vitro angiogenesis of primary endothelial cells. BRs constitute a novel group of human steroid receptor activators or inhibitors with capacity to inhibit angiogenesis.

• MeSH
• alfa receptor estrogenů metabolismus   MeSH
• beta receptor estrogenů metabolismus   MeSH
• brassinosteroidy metabolismus   farmakologie   MeSH
• endoteliální buňky pupečníkové žíly (lidské) účinky léků   metabolismus   MeSH
• fyziologická neovaskularizace účinky léků   MeSH
• inhibitory angiogeneze metabolismus   farmakologie   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Estrogen replacement therapy could play a role in the reduction of injury associated with cerebral ischemia in vivo, which could be, at least partially, a consequence of estrogen influence of glutamate buffering by astrocytes during hypoxia/ischemia. Estrogen exerts biological effects through interaction with its two receptors: estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), which are both expressed in astrocytes. This study explored effects of hypoxia and glucose deprivation (HGD), alone or followed by 1 h recovery, on ERα and ERβ expression in primary rat astrocyte cultures following 1 h exposure to: a) 5 % CO2 in air (control group-CG); b) 2 % O2/5 % CO2 in N2 with glucose deprivation (HGD group-HGDG); or c) the HGDG protocol followed by 1 h CG protocol (recovery group-RG). ERα mRNA expression decreased in HGDG. At the protein level, full-length ERα (67 kDa) and three ERα-immunoreactive protein bands (63, 60 and 52 kDa) were detected. A significant decrease in the 52 kDa band was seen in HGDG, while a significant decrease in expression of the full length ERα was seen in the RG. ERβ mRNA and protein expression (a 54 kDa single band) did not change. The observed decrease in ERα protein may limit estrogenmediated signalling in astrocytes during hypoxia and recovery.

• MeSH
• alfa receptor estrogenů genetika   metabolismus   MeSH
• astrocyty metabolismus   MeSH
• beta receptor estrogenů genetika   metabolismus   MeSH
• glukosa metabolismus   MeSH
• hypoxie buňky MeSH
• krysa rodu rattus MeSH
• messenger RNA metabolismus   MeSH
• potkani Sprague-Dawley MeSH
• primární buněčná kultura MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

The role of oestrogen in oncogenesis has been examined extensively, especially in the context of breast cancer, and receptor modulators are an integral part of targeted treatment in this disease. The role of oestrogen signalling in colonic carcinoma is poorly understood. Men are more susceptible than women to colon cancer. Furthermore, hormone-replacement therapy affords an additive protective effect for postmenopausal women, and when these women do develop cancer, they typically have less aggressive disease. The discovery of a second oestrogen receptor (ERbeta) and its over expression in healthy human colon coupled with reduced expression in colon cancer suggests that this receptor might be involved. The underlying mechanism, however, remains largely unknown. In this Review, we discuss the various hypotheses presented in the published literature. We examine the cellular and molecular mechanisms through which oestrogen is purported to exert its protective influence, and we review the evidence available to support these claims.

• MeSH
• beta receptor estrogenů genetika   metabolismus   MeSH
• hodnocení rizik MeSH
• imunohistochemie MeSH
• incidence MeSH
• jehlová biopsie MeSH
• lidé MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádory prsu epidemiologie   patologie   prevence a kontrola   MeSH
• nádory tračníku epidemiologie   patologie   prevence a kontrola   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• prognóza MeSH
• receptory pro estrogeny genetika   metabolismus   MeSH
• senzitivita a specificita MeSH
• střevní sliznice patologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• srovnávací studie MeSH