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 pathogenesis of adolescent idiopathic scoliosis (AIS), including the associated local changes in deep paravertebral muscles, is poorly understood. The asymmetric expression of several molecules involved in the melatonin signaling pathway, including melatonin receptors 1A/1B (MTNR1A/MTNR1B), estrogen receptor 2 (ESR2) and calmodulin (CALM1), has previously been suggested to be associated with AIS. However, this hypothesis is based on single studies in which the data were obtained by different methodological approaches. Therefore, to evaluate the symmetry of the mRNA expression levels of these molecules, 18 patients with AIS and 10 non‑scoliotic controls were enrolled in the present study. Muscle biopsy samples from deep paraspinal muscles (from the convexity and concavity of the scoliotic curve in patients with AIS, or from the left and right sides in controls) were obtained during spinal surgery. For each sample, the relative mRNA expression levels of MTNR1A, MTNR1B, CALM1 and ESR2 were analyzed by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and were quantified according to the quantification cycle method. The results indicated that the mRNA expression levels of none of the investigated molecules were significantly different between samples obtained from the convex and concave side of the scoliotic curve in patients with AIS. In addition, no difference in expression was detected between the patients with AIS and the controls. With regards to MTNR1A and MTNR1B, their expression was very weak in paravertebral muscles, and in the majority of cases their expression could not be detected by repeated RT‑qPCR analysis. Therefore, these data do not support the previously suggested role of the asymmetric expression of molecules involved in the melatonin signaling pathway in deep paravertebral muscles in the pathogenesis of AIS.
- MeSH
- beta receptor estrogenů genetika MeSH
- dítě MeSH
- dospělí MeSH
- exprese genu MeSH
- genetická predispozice k nemoci MeSH
- hluboké zádové svaly metabolismus MeSH
- kalmodulin genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA MeSH
- mladiství MeSH
- mladý dospělý MeSH
- receptor melatoninový MT1 genetika MeSH
- receptor melatoninový MT2 genetika MeSH
- skolióza etiologie metabolismus patologie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Steroid receptor coactivators p300 and CBP are highly expressed in advanced prostate cancer. They potentiate activation of androgen receptor by androgens and anti-androgens. In the present study, we have addressed the question whether these coactivators enhance activity of estrogen receptor-beta (ER-β), which is variably expressed in prostate cancers. METHODS: Expression levels of the coactivators p300 and CBP were manipulated by plasmid or siRNA transfections and activity of ER-β was measured by luciferase assays. Viability was measured by MTT assays and cellular migration was determined by wound-healing and Boyden chamber assays. RESULTS: High expression of ER-β was found in PC3 cells which were used for the experiments. p300 or CBP enhanced activation of ER-β by genistein. Antiestrogens did not acquire agonistic properties in the presence of increased concentrations of either coactivator. Inhibition of p300 or CBP decreased genistein stimulation of ER-β. Genistein reduced migration of PC3 prostate cancer cells and down-regulation of p300 potentiated this effect. CONCLUSIONS: p300 and CBP are implicated in regulation of ER-β activity and cellular migration in prostate cancer. These findings are important for understanding of action of ER-β in carcinoma of the prostate.
- MeSH
- beta receptor estrogenů genetika fyziologie MeSH
- genistein farmakologie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory prostaty patologie MeSH
- pohyb buněk účinky léků MeSH
- protein p300 asociovaný s E1A fyziologie MeSH
- protein vázající CREB fyziologie MeSH
- signální transdukce MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví 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
To identify novel estrogen receptor ligands a series of substituted 17alpha-arylestradiols were synthesized using the catalytic [2 + 2 + 2]cyclotrimerization of 17alpha-ethynylestradiol with various 1,7-diynes in the presence of Wilkinson's catalysts [Rh(PPh(3))(3)Cl]. The compounds were subjected to competitive binding assays, cell-based luciferase reporter assays, and proliferation assays. These experiments confirmed their estrogenic character and revealed some interesting properties like mixed partial/full agonism for ERalpha/ERbeta and different selectivity as a result of differing potencies for either ER.
- MeSH
- aktivace transkripce MeSH
- alfa receptor estrogenů agonisté genetika MeSH
- alkyny chemie MeSH
- beta receptor estrogenů agonisté genetika MeSH
- buněčné linie MeSH
- cyklizace MeSH
- estradiol analogy a deriváty chemická syntéza farmakologie MeSH
- fluorescenční polarizace MeSH
- kompetitivní vazba MeSH
- lidé MeSH
- ligandy MeSH
- luciferasy genetika MeSH
- nádorové buněčné linie MeSH
- parciální agonismus léků MeSH
- proliferace buněk účinky léků MeSH
- reportérové geny MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- 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
- MeSH
- běloši genetika MeSH
- beta receptor estrogenů genetika MeSH
- dospělí MeSH
- jednonukleotidový polymorfismus MeSH
- kostní denzita MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidské chromozomy, pár 14 MeSH
- lokus kvantitativního znaku MeSH
- vazebná nerovnováha MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- souhrny MeSH
- MeSH
- beta receptor estrogenů genetika imunologie MeSH
- chinazoliny terapeutické užití MeSH
- geny erbB genetika imunologie MeSH
- hormonální protinádorové látky terapeutické užití MeSH
- lidé MeSH
- nádory prsu farmakoterapie terapie MeSH
- nemalobuněčný karcinom plic farmakoterapie terapie MeSH
- prognóza MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- Check Tag
- lidé MeSH