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Androgen regulation, sinalization and cellular interactions in prostate development, physiology and regression

Grant number: 09/16150-6
Support type:Research Projects - Thematic Grants
Duration: October 01, 2010 - September 30, 2015
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal researcher:Hernandes Faustino de Carvalho
Grantee:Hernandes Faustino de Carvalho
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Assoc. researchers:Carmen Veríssima Ferreira ; Catarina Segreti Porto ; Dagmar Ruth Stach - Machado ; João de Jesus Viana Pinheiro ; José Barreto Campello Carvalheira ; Leonardo Oliveira Reis ; Luciana Bolsoni Lourenço ; Maria Aparecida da Silva Pinhal ; Maria Beny Pinto Zakia ; Maria Cristina Cintra Gomes Marcondes ; Patrícia Gama ; Renato Vicentini dos Santos ; Ruy Gastaldoni Jaeger ; Sara Teresinha Olalla Saad ; Sérgio Luis Felisbino ; Simone Cristina Olenscki Gilli ; Vanessa Morais Freitas ; Willian Fernando Zambuzzi
Associated grant(s):14/17188-5 - 2014 ASCB/IFCB Meeting, AR.EXT
Associated scholarship(s):15/17791-6 - Localization and function of the ABCC3 transporter in the prostate gland: androgen regulation and role in the protection against carcinogens, BP.IC
15/03235-4 - Prostatic smooth muscle cells: regulation of differentiation and activation of focal adhesion kinase (FAK)by interactions with the epithelium and the extracelluar matrix, BP.DR
15/03599-6 - Evaluation of the role of TGF-² signaling pathway in prostatic induction: from the urogenital sinus to the ventral prostate primordium in mice and characterization of similar transitions in RWPE-1 cells, BP.PD
+ associated scholarships 14/23528-3 - RWPE-1 cells: correlation between the expression of p63 and the androgen receptor (AR), BP.PD
14/22225-7 - Relation between the expression of p63 and androgen receptor in the rat ventral prostate and in RWPE-1 cells, BP.PD
13/22071-7 - Exploring new molecules and their interactions in prostate biology, BP.PD
12/17657-0 - Heparanase activity and its role in the modulation of extracellular signaling in prostate development, BP.DD
12/07512-4 - Sequential gene expression in response to androgen deprivation: orchestrating secretion activity, proliferation and cell death in the rat ventral prostate, BP.DR
11/19288-9 - Mucosal immunology exploration in the prospection of a vaccine prototype for genitourinary infections: directing the immune response to the prostate gland - preclinical study, BP.PD
11/08559-1 - Heparanase-1 participation in the invasive capacity of tumor prostate cells, BP.PD - associated scholarships


The control of prostatic growth and functioning is based on a complex network of interactions between steroid hormones and their receptors, as well as on an intricate mechanism of interconversion among them, paralleled by epithelial-stromal interactions mediated by paracrine factors. The androgens testosterone and dihydrotestosterone are the major regulators of prostatic development and function, acting via androgen receptor (AR). Estrogens also play important roles in normal prostate, but appear as important endocrine disruptor, acting both systemically and locally besides promoting estrogen imprinting. Interactions between the epithelial cells and stromal cells (mostly smooth muscle cells and fibroblast, but also endothelial cells and cells of the immune system, with an intimate participation of the extracellular matrix and its receptors are important in these aspects. Besides, the prostate is the local of many diseases, including prostatites and benign and malignant neoplasias, which result in the death of a vast number of male individuals, especially in the elder. Components of the diet, in special fatty acids contribute to the incidence and progression of prostatic tumors. In spite of the importance of the gland and of the large number of studies on it, little is known about prostatic immunology and its role in tumor progression or in the regression attained by castration. This project aims at extending our knowledge of the prostate gland, approaching the aspects mentioned above, gathering a multidisciplinary team and a wide spectrum of methodologies for the biochemical, cellular and molecular analysis of the prostate gland, extending and exploring earlier studies from our group. Furthermore, we also aim at exploring factors allowing for the use of the prostate gland, its cells and regulatory mechanisms as biosensors, tools for immunization against infections of the genitor-urinary tract, or for the intervention or treatment of prostate cancer. (AU)

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Scientific publications (24)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
NISHAN, UMAR; ROSA-RIBEIRO, RAFAELA; CESAR, CARLOS LENZ; CARVALHO, HERNANDES F.. Transcription regulators are transiently expressed during the prostate gland adaptation to the hypoandrogenic environment. HISTOLOGY AND HISTOPATHOLOGY, v. 34, n. 9, p. 1025-1036, . (09/16150-6)
OLIVEIRA, ELUSA CRISTINA; LEONELLI, CARINA; PEREIRA, ODUVALDO C. M.; BITTENCOURT, JACKSON C.; CARVALHO, HERNANDES F.. Estrogen imprinting compromises male sexual behavior and affects the number of androgen-receptor-expressing hypothalamic neurons. BIOLOGY OF REPRODUCTION, v. 100, n. 3, p. 737-744, . (09/16150-6)
SANCHES, BRUNO D. A.; CARVALHO, HERNANDES F.; MALDARINE, JULIANA S.; BIANCARDI, MANOEL F.; SANTOS, FERNANDA C. A.; VILAMAIOR, PATRICIA S. L.; TABOGA, SEBASTIAO R.. Differences between male and female prostates in terms of physiology, sensitivity to chemicals and pathogenesis-A review in a rodent model. Cell Biology International, . (09/16150-6, 18/23383-6)
BARBOSA, GUILHERME OLIVEIRA; AUGUSTO, TAIZE MACHADO; BRUNI-CARDOSO, ALEXANDRE; CARVALHO, HERNANDES F.. The role of SDF1 in prostate epithelial morphogenesis. Journal of Cellular Physiology, v. 234, n. 5, p. 6886-6897, . (12/17657-0, 09/16150-6, 14/18103-3)
DAMAS-SOUZA, DANILO M.; NUNES, RONY; CARVALHO, HERNANDES F.. An improved acridine orange staining of DNA/RNA. ACTA HISTOCHEMICA, v. 121, n. 4, p. 450-454, . (14/50938-8, 09/16150-6)
SOLIS-CALERO, CHRISTIAN; ZANATTA, GEANCARLO; DO O PESSOA, CLAUDIA; CARVALHO, HERNANDES F.; FREIRE, VALDER N.. Explaining urokinase type plasminogen activator inhibition by amino-5-hydroxybenzimidazole and two naphthamidine-based compounds through quantum biochemistry. Physical Chemistry Chemical Physics, v. 20, n. 35, p. 22818-22830, . (09/16150-6)
SILVA, JULIETE A. F.; BRUNI-CARDOSO, ALEXANDRE; AUGUSTO, TAIZE M.; DAMAS-SOUZA, DANILO M.; BARBOSA, GUILHERME O.; FELISBINO, SERGIO L.; STACH-MACHADO, DAGMAR R.; CARVALHO, HERNANDES F.. Macrophage roles in the clearance of apoptotic cells and control of inflammation in the prostate gland after castration. PROSTATE, v. 78, n. 2, p. 95-103, . (09/16150-6, 14/50938-8)
MORAIS, PABLO A.; MAIA, JR., FRANCISCO FRANCINE; SOLIS-CALERO, CHRISTIAN; SANTOS CAETANO, EWERTON WAGNER; FREIRE, VALDER NOGUEIRA; CARVALHO, HERNANDES F.. The urokinase plasminogen activator binding to its receptor: a quantum biochemistry description within an in/homogeneous dielectric function framework with application to uPA-uPAR peptide inhibitors. Physical Chemistry Chemical Physics, v. 22, n. 6, p. 3570-3583, . (14/50938-8, 09/16150-6)
BARBOSA, GUILHERME O.; BIANCARDI, MANOEL F.; CARVALHO, HERNANDES F.. Heparan sulfate fine-tunes stromal-epithelial communication in the prostate gland. DEVELOPMENTAL DYNAMICS, v. 250, n. 5, p. 618-628, . (09/16150-6)
SOLIS-CALERO, CHRISTIAN; CARVALHO, HERNANDES F.. KLK14 interactions with HAI-1 and HAI-2 serine protease inhibitors: A molecular dynamics and relative free-energy calculations study. Cell Biology International, v. 41, n. 11, SI, p. 1246-1264, . (09/16150-6)
ADUR, J.; BARBOSA, G. O.; PELEGATI, V. B.; BARATTI, M. O.; CESAR, C. L.; CASCO, V. H.; CARVALHO, H. F.. Multimodal and Non-Linear Optical Microscopy Applications in Reproductive Biology. MICROSCOPY RESEARCH AND TECHNIQUE, v. 79, n. 7, p. 567-582, . (09/16150-6)
BARBUTTI, ISABELLA; LAURENTINO, JESSE C.; VA DA SILVA, NATALIA; DEOCLECIO, VINICIUS S.; FERRUCCI, DANILO; CARVALHO, HERNANDES F.. Dietary Fat Quality in Normolipidic Diets Affects Hepatocyte's Nuclear Phenotypes. NUTRITION AND METABOLIC INSIGHTS, v. 13, . (14/50938-8, 09/16150-6)
FERRUCCI, DANILO; SILVA, SILAS PINTO; ROCHA, ANDR; NASCIMENTO, LUCAS; VIEIRA, ANDRE SCHWAMBACH; TABOGA, SEBASTIAO ROBERTO; MORI, MARCELO; LENZ-CESAR, CARLOS; CARVALHO, HERNANDES F.. Dietary fatty acid quality affects systemic parameters and promotes prostatitis and pre-neoplastic lesions. SCIENTIFIC REPORTS, v. 9, . (14/50938-8, 09/16150-6, 17/04377-2)
UMAR NISHAN; RAFAELA DA ROSA-RIBEIRO; DANILO MARCHETE DAMAS-SOUZA; GUILHERME OLIVEIRA BARBOSA; HERNANDES F. CARVALHO. Transcriptional regulators and regulatory pathways involved in prostate gland adaptation to a hypoandrogen environment. GENETICS AND MOLECULAR BIOLOGY, v. 42, n. 4, . (09/16150-6)
AUGUSTO, TAIZE M.; ROSA-RIBEIRO, RAFAELA; CARVALHO, HERNANDES F.. Neonatal exposure to high doses of 17 beta-estradiol results in inhibition of heparanase-1 expression in the adult prostate. Histochemistry and Cell Biology, v. 136, n. 5, p. 609-615, . (09/16150-6)
CAIRES-DOS-SANTOS, LIVIA; DA SILVA, SUELY V.; SMUCZEK, BASILIO; DE SIQUEIRA, ADRIANE S.; CRUZ, KAREN S. P.; BARBUTO, JOSE ALEXANDRE M.; AUGUSTO, TAIZE M.; FREITAS, VANESSA M.; CARVALHO, HERNANDES F.; JAEGER, RUY G.. Laminin-derived peptide C16 regulates Tks expression and reactive oxygen species generation in human prostate cancer cells. Journal of Cellular Physiology, v. 235, n. 1, . (09/16150-6, 15/03393-9, 10/07699-1, 18/03528-0, 09/17336-6)
SANCHES, BRUNO D. A.; CARVALHO, HERNANDES F.; MALDARINE, JULIANA S.; BIANCARDI, MANOEL F.; SANTOS, FERNANDA C. A.; VILAMAIOR, PATRICIA S. L.; TABOGA, SEBASTIAO R.. Differences between male and female prostates in terms of physiology, sensitivity to chemicals and pathogenesis-A review in a rodent model. Cell Biology International, v. 44, n. 1, p. 27-35, . (09/16150-6, 18/23383-6)
BARBOSA, GUILHERME O.; SILVA, JULIETE A. F.; SIQUEIRA-BERTI, ALINE; NISHAN, UMAR; ROSA-RIBEIRO, RAFAELA; OLIVEIRA, SILVIA B. P.; BARATTI, MARIANA O.; FERRUCCI, DANILO; SANTANA, JULIO C. O.; DAMAS-SOUZA, DANILO M.; et al. Castration-induced prostate epithelial cell apoptosis results from targeted oxidative stress attack of M1(142)-macrophages. Journal of Cellular Physiology, v. 234, n. 10, p. 19048-19058, . (09/16150-6)
SOLIS-CALERO, CHRISTIAN; AUGUSTO, TAIZE M.; CARVALHO, HERNANDES F.. Human-specific features of the G-quadruplex in the androgen receptor gene promoter: A comparative structural and dynamics study. JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, v. 182, p. 95-105, . (09/16150-6)
BARBOSA, GUILHERME OLIVEIRA; BRUNI-CARDOSO, ALEXANDRE; DA SILVA PINHAL, MARIA APARECIDA; AUGUSTO, TAIZE MACHADO; CARVALHO, HERNANDES F.. Heparanase-1 activity and the early postnatal prostate development. DEVELOPMENTAL DYNAMICS, v. 248, n. 3, p. 211-220, . (09/16150-6, 12/17657-0)
SOLIS-CALERO, CHRISTIAN; CARVALHO, HERNANDES F.. Phylogenetic, molecular evolution and structural analyses of the WFDC1/prostate stromal protein 20 (ps20). Gene, v. 686, p. 125-140, . (09/16150-6)
ROSA-RIBEIRO, RAFAELA; BARBOSA, GUILHERME OLIVEIRA; KUEHNE, FABIANA; CARVALHO, HERNANDES F.. Desquamation is a novel phenomenon for collective prostate epithelial cell deletion after castration. Histochemistry and Cell Biology, v. 141, n. 2, p. 213-220, . (09/16150-6, 08/07990-8)
SILVA, JULIETE A. F.; BIANCARDI, MANOEL F.; STACH-MACHADO, DAGMAR R.; REIS, LEONARDO O.; SANT'ANNA, OSVALDO A.; CARVALHO, HERNANDES F.. The origin of prostate gland-secreted IgA and IgG. SCIENTIFIC REPORTS, v. 7, . (13/07467-1, 09/16150-6)
ROSA-RIBEIRO, RAFAELA; NISHAN, UMAR; VIDAL, RAMON OLIVEIRA; BARBOSA, GUILHERME OLIVEIRA; REIS, LEONARDO OLIVEIRA; CESAR, CARLOS LENZ; CARVALHO, HERNANDES F.. Transcription Factors Involved in Prostate Gland Adaptation to Androgen Deprivation. PLoS One, v. 9, n. 6, . (09/16150-6)

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