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  1. Article: Molecular regulation of prostate cancer by Galectin-3 and estrogen receptor.

    Souza, Deborah Simão / Macheroni, Carla / Pereira, Gustavo José Silva / Vicente, Carolina Meloni / Porto, Catarina Segreti

    Frontiers in endocrinology

    2023  Volume 14, Page(s) 1124111

    Abstract: Prostate cancer remains the most prevalent cancer among men worldwide. This cancer is hormone-dependent; therefore, androgen, estrogen, and their receptors play an important role in development and progression of this disease, and in emergence of the ... ...

    Abstract Prostate cancer remains the most prevalent cancer among men worldwide. This cancer is hormone-dependent; therefore, androgen, estrogen, and their receptors play an important role in development and progression of this disease, and in emergence of the castration-resistant prostate cancer (CRPC). Galectins are a family of β-galactoside-binding proteins which are frequently altered (upregulated or downregulated) in a wide range of tumors, participating in different stages of tumor development and progression, but the molecular mechanisms which regulate its expression are still poorly understood. This review provides an overview of the current and emerging knowledge on Galectin-3 in cancer biology with focus on prostate cancer and the interplay with estrogen receptor (ER) signaling pathways, present in androgen-independent prostate cancer cells. We suggest a molecular mechanism where ER, Galectin-3 and β-catenin can modulate nuclear transcriptional events, such as, proliferation, migration, invasion, and anchorage-independent growth of androgen-independent prostate cancer cells. Despite a number of achievements in targeted therapy for prostate cancer, CRPC may eventually develop, therefore new effective drug targets need urgently to be found. Further understanding of the role of Galectin-3 and ER in prostate cancer will enhance our understanding of the molecular mechanisms of prostate cancer development and the future treatment of this disease.
    MeSH term(s) Male ; Humans ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/metabolism ; Prostatic Neoplasms, Castration-Resistant/pathology ; Receptors, Estrogen ; Galectin 3/genetics ; Androgens/therapeutic use ; Receptors, Androgen/metabolism ; Galectins
    Chemical Substances Receptors, Estrogen ; Galectin 3 ; Androgens ; Receptors, Androgen ; Galectins
    Language English
    Publishing date 2023-03-03
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2023.1124111
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: The role of estrogen receptors in rat Sertoli cells at different stages of development.

    Macheroni, Carla / Lucas, Thaís Fabiana Gameiro / Porto, Catarina Segreti

    Heliyon

    2020  Volume 6, Issue 11, Page(s) e05363

    Abstract: The aim of the study was to investigate the effects of estrogen receptors (ESR1 and ESR2) on the expression of the proteins involved with proliferation (CCND1) and differentiation (CDKN1B and CTNNB) of Sertoli cells from rat in different stages of ... ...

    Abstract The aim of the study was to investigate the effects of estrogen receptors (ESR1 and ESR2) on the expression of the proteins involved with proliferation (CCND1) and differentiation (CDKN1B and CTNNB) of Sertoli cells from rat in different stages of development. ESR1-selective agonist PPT, but not ESR2-selective agonist DPN, increased CCND1 expression in Sertoli cells from 5- and 15-day old rats. PPT did not have any effect on CCND1 expression in Sertoli cells from 20- and 30-day-old rats. DPN, but not PPT, increased CDKN1B expression in Sertoli cells from 15-, 20-, 30-day-old rats. DPN did not have any effect on Sertoli cells from 5-day-old rats. 17β-estradiol (E2) and PPT enhanced the [Methyl-
    Language English
    Publishing date 2020-11-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 2835763-2
    ISSN 2405-8440
    ISSN 2405-8440
    DOI 10.1016/j.heliyon.2020.e05363
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Estrogen receptors regulate galectin‑3 in androgen‑independent DU‑145 prostate cancer cells.

    Souza, Deborah S / Macheroni, Carla / Vicente, Carolina M / Cavalheiro, Renan P / Campo, Vanessa L / Porto, Catarina S

    Oncology reports

    2023  Volume 49, Issue 5

    Abstract: The aim of the present study was to investigate the role of estrogen receptor (ER)α and ERβ, and galectin‑3 (GAL‑3) in migration and invasion of androgen‑independent DU‑145 prostate cancer cells, and to examine the regulation of the expression of GAL‑3 ... ...

    Abstract The aim of the present study was to investigate the role of estrogen receptor (ER)α and ERβ, and galectin‑3 (GAL‑3) in migration and invasion of androgen‑independent DU‑145 prostate cancer cells, and to examine the regulation of the expression of GAL‑3 by the activation of these receptors. Wound healing and cell invasion assays were performed using the control (basal level of cellular function) and treated DU‑145 cells. At 24 h of treatment, 17β‑estradiol (E2), the ERα‑selective agonist, 4,4',4"‑(4‑propyl‑(1H)‑pyrazole‑1,3,5‑triyl)trisphenol (PPT), or the ERβ‑selective agonist, 2,3‑bis(4‑hydroxyphenyl)‑propionitrile (diarylprepionitrile; DPN), increased the migration and invasion of the DU‑145 cells. Pre‑treatment with the ERα‑ and ERβ‑selective antagonists blocked these effects, indicating that ERα and ERβ are upstream receptors regulating these processes. Western blot analysis and immunofluorescence staining for the detection of the GAL‑3 were performed using the control and treated DU‑145 cells. Treatment of the DU‑145 cells with E2, PPT or DPN for 24 h increased the expression of the GAL‑3 compared to the control. Furthermore, a specific inhibitor of GAL‑3 (VA03) inhibited the migration and invasion of DU‑145 cells, indicating the involvement of the complex ERα/GAL‑3 and ERβ/GAL‑3 in the regulation of these processes. On the whole, the present study demonstrates that the activation of both ERs increases the expression and signaling of GAL‑3, and promotes the migration and invasion of DU‑145 cells. The findings of the present study provide novel insight into the signatures and molecular mechanisms of ERα and ERβ in DU‑145 cells.
    MeSH term(s) Male ; Humans ; Receptors, Estrogen ; Estrogen Receptor alpha/metabolism ; Galectin 3 ; Androgens ; Estrogen Receptor beta/genetics ; Estrogen Receptor beta/metabolism ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/metabolism ; Estradiol/pharmacology
    Chemical Substances Receptors, Estrogen ; Estrogen Receptor alpha ; Galectin 3 ; Androgens ; Estrogen Receptor beta ; Estradiol (4TI98Z838E)
    Language English
    Publishing date 2023-03-24
    Publishing country Greece
    Document type Journal Article
    ZDB-ID 1222484-4
    ISSN 1791-2431 ; 1021-335X
    ISSN (online) 1791-2431
    ISSN 1021-335X
    DOI 10.3892/or.2023.8530
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Activation of estrogen receptor induces differential proteomic responses mainly involving migration, invasion, and tumor development pathways in human testicular embryonal carcinoma NT2/D1 cells.

    Macheroni, Carla / Leite, Giuseppe Gianini Figueirêdo / Souza, Deborah Simão / Vicente, Carolina Meloni / Lacerda, José Thalles / Moraes, Maria Nathália / Juliano, Maria Aparecida / Porto, Catarina Segreti

    The Journal of steroid biochemistry and molecular biology

    2023  Volume 237, Page(s) 106443

    Abstract: The aims of the present study were to investigate the global changes on proteome of human testicular embryonal carcinoma NT2/D1 cells treated with 17β-estradiol (E2), and the effects of this hormone on migration, invasion, and colony formation of these ... ...

    Abstract The aims of the present study were to investigate the global changes on proteome of human testicular embryonal carcinoma NT2/D1 cells treated with 17β-estradiol (E2), and the effects of this hormone on migration, invasion, and colony formation of these cells. A quantitative proteomic analysis identified the presence of 1230 proteins in both E2-treated and control cells. The analysis revealed 75 differentially abundant proteins (DAPs), out of which 43 proteins displayed a higher abundance and, 30 proteins showed a lower abundance in E2-treated NT2/D1 cancer cells. Functional analysis using IPA highlighted some activation processes such as migration, invasion, metastasis, and tumor growth. Interestingly, the treatment with E2 and ERβ-selective agonist DPN increased the migration of NT2/D1 cells. On the other hand, ERα-selective agonist PPT did not modify cell migration, indicating that ERβ is the upstream receptor involved in this process. The activation of ERβ increased the invasion and anchorage‑independent growth of NT2/D1 cells more intensely than ERα. ERα and ERβ may play overlapping roles on invasion and colony formation of these cells. Further studies are required to clarify the mechanism underlying these effects. The molecular mechanisms revealed by proteomic and functional studies might also guide the development of potential targets for a better understanding of the biology of these cells and novel treatments for non-seminoma in the future.
    MeSH term(s) Humans ; Receptors, Estrogen ; Carcinoma, Embryonal ; Estrogen Receptor alpha/genetics ; Estrogen Receptor alpha/metabolism ; Estrogen Receptor beta/metabolism ; Proteomics ; Estradiol/pharmacology
    Chemical Substances Receptors, Estrogen ; Estrogen Receptor alpha ; Estrogen Receptor beta ; Estradiol (4TI98Z838E)
    Language English
    Publishing date 2023-12-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1049188-0
    ISSN 1879-1220 ; 0960-0760
    ISSN (online) 1879-1220
    ISSN 0960-0760
    DOI 10.1016/j.jsbmb.2023.106443
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Activation of estrogen receptor ESR1 and ESR2 induces proliferation of the human testicular embryonal carcinoma NT2/D1 cells.

    Macheroni, Carla / Gameiro Lucas, Thaís Fabiana / Souza, Deborah Simão / Vicente, Carolina Meloni / Pereira, Gustavo José da Silva / Junior, Itabajara da Silva Vaz / Juliano, Maria Aparecida / Porto, Catarina Segreti

    Molecular and cellular endocrinology

    2022  Volume 554, Page(s) 111708

    Abstract: The aims of the present study were to investigate the expression of the classic estrogen receptors ESR1 and ESR2, the splicing variant ESR1-36 and GPER in human testicular embryonal carcinoma NT2/D1 cells, and the effects of the activation of the ESR1 ... ...

    Abstract The aims of the present study were to investigate the expression of the classic estrogen receptors ESR1 and ESR2, the splicing variant ESR1-36 and GPER in human testicular embryonal carcinoma NT2/D1 cells, and the effects of the activation of the ESR1 and ESR2 on cell proliferation. Immunostaining of ESR1, ESR2, and GPER were predominantly found in the nuclei, and less abundant in the cytoplasm. ESR1-36 isoform was predominantly expressed in the perinuclear region and cytoplasm, and some weakly immunostained in the nuclei. In nonstimulated NT2/D1 cells (control), proteins of the cell cycle CCND1, CCND2, CCNE1 and CDKN1B are present. Activation of ESR1 and ESR2 increases, respectively, CCND2 and CCNE1 expression, but not CCND1. Activation of ESR2 also mediates upregulation of the cell cycle inhibitor CDKN1B. This protein co-immunoprecipitated with CCND2. Also, E2 induces an increase in the number and viability of the NT2/D1 cells. These effects are blocked by simultaneous pretreatment with ESR1-and ESR2-selective antagonists, confirming that both estrogen receptors regulate NT2/D1 cell proliferation. In addition, E2 increases SRC phosphorylation, and SRC mediates cell proliferation. Our study provides novel insights into the signatures and molecular mechanisms of estrogen receptor in NT2/D1 cells.
    MeSH term(s) Carcinoma, Embryonal ; Cell Proliferation ; Estrogen Receptor alpha/metabolism ; Estrogen Receptor beta/genetics ; Estrogen Receptor beta/metabolism ; Humans ; Phosphorylation ; Receptors, Estrogen/metabolism
    Chemical Substances ESR1 protein, human ; ESR2 protein, human ; Estrogen Receptor alpha ; Estrogen Receptor beta ; Receptors, Estrogen
    Language English
    Publishing date 2022-07-02
    Publishing country Ireland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 187438-x
    ISSN 1872-8057 ; 0303-7207
    ISSN (online) 1872-8057
    ISSN 0303-7207
    DOI 10.1016/j.mce.2022.111708
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Activation of estrogen receptor ESR1 and ESR2 induces proliferation of the human testicular embryonal carcinoma NT2/D1 cells

    Macheroni, Carla / Gameiro Lucas, Thaís Fabiana / Souza, Deborah Simão / Vicente, Carolina Meloni / Pereira, Gustavo José da Silva / Junior, Itabajara da Silva Vaz / Juliano, Maria Aparecida / Porto, Catarina Segreti

    Molecular and cellular endocrinology. 2022 Aug. 20, v. 554

    2022  

    Abstract: The aims of the present study were to investigate the expression of the classic estrogen receptors ESR1 and ESR2, the splicing variant ESR1-36 and GPER in human testicular embryonal carcinoma NT2/D1 cells, and the effects of the activation of the ESR1 ... ...

    Abstract The aims of the present study were to investigate the expression of the classic estrogen receptors ESR1 and ESR2, the splicing variant ESR1-36 and GPER in human testicular embryonal carcinoma NT2/D1 cells, and the effects of the activation of the ESR1 and ESR2 on cell proliferation. Immunostaining of ESR1, ESR2, and GPER were predominantly found in the nuclei, and less abundant in the cytoplasm. ESR1-36 isoform was predominantly expressed in the perinuclear region and cytoplasm, and some weakly immunostained in the nuclei. In nonstimulated NT2/D1 cells (control), proteins of the cell cycle CCND1, CCND2, CCNE1 and CDKN1B are present. Activation of ESR1 and ESR2 increases, respectively, CCND2 and CCNE1 expression, but not CCND1. Activation of ESR2 also mediates upregulation of the cell cycle inhibitor CDKN1B. This protein co-immunoprecipitated with CCND2. Also, E2 induces an increase in the number and viability of the NT2/D1 cells. These effects are blocked by simultaneous pretreatment with ESR1-and ESR2-selective antagonists, confirming that both estrogen receptors regulate NT2/D1 cell proliferation. In addition, E2 increases SRC phosphorylation, and SRC mediates cell proliferation. Our study provides novel insights into the signatures and molecular mechanisms of estrogen receptor in NT2/D1 cells.
    Keywords carcinoma ; cell cycle ; cell proliferation ; cytoplasm ; estrogen receptors ; estrogens ; humans ; phosphorylation ; testes ; viability
    Language English
    Dates of publication 2022-0820
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 187438-x
    ISSN 1872-8057 ; 0303-7207
    ISSN (online) 1872-8057
    ISSN 0303-7207
    DOI 10.1016/j.mce.2022.111708
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: Crosstalk between FSH and relaxin at the end of the proliferative stage of rat Sertoli cells.

    Nascimento, Aline R / Macheroni, Carla / Lucas, Thais F G / Porto, Catarina S / Lazari, Maria F M

    Reproduction (Cambridge, England)

    2016  Volume 152, Issue 6, Page(s) 613–628

    Abstract: Follicle-stimulating hormone (FSH) stimulates the proliferation of immature Sertoli cells through the activation of PI3K/AKT/mTORC1 and MEK/ERK1/2 pathways. Mature Sertoli cells stop proliferating and respond to FSH by stimulating cAMP production. To ... ...

    Abstract Follicle-stimulating hormone (FSH) stimulates the proliferation of immature Sertoli cells through the activation of PI3K/AKT/mTORC1 and MEK/ERK1/2 pathways. Mature Sertoli cells stop proliferating and respond to FSH by stimulating cAMP production. To gain insight into possible mechanisms involved in this switch as well as the impact of paracrine factors that stimulate cell proliferation, we analyzed the effects of FSH and relaxin on intracellular signaling pathways involved with proliferation and differentiation in Sertoli cells from 15-day-old rats, which are close to the transition between the two stages. FSH stimulated
    MeSH term(s) Animals ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Cell Differentiation/drug effects ; Cell Proliferation/drug effects ; Cells, Cultured ; Follicle Stimulating Hormone/pharmacology ; Gene Expression Regulation/drug effects ; Hormones/pharmacology ; Male ; Phosphorylation/drug effects ; Rats ; Rats, Wistar ; Relaxin/pharmacology ; Sertoli Cells/cytology ; Sertoli Cells/drug effects ; Sertoli Cells/metabolism ; Signal Transduction/drug effects
    Chemical Substances Cell Cycle Proteins ; Hormones ; Follicle Stimulating Hormone (9002-68-0) ; Relaxin (9002-69-1)
    Language English
    Publishing date 2016-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 2034501-X
    ISSN 1741-7899 ; 1470-1626 ; 1476-3990
    ISSN (online) 1741-7899
    ISSN 1470-1626 ; 1476-3990
    DOI 10.1530/REP-16-0330
    Database MEDical Literature Analysis and Retrieval System OnLINE

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