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

• Grant number: 09/16150-6
• Support Opportunities: Research Projects - Thematic Grants
• Start date: October 01, 2010
• End date: September 30, 2015
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Hernandes Faustino de Carvalho
• Grantee: Hernandes Faustino de Carvalho
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated 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 research 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

Abstract

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)

Scientific publications

(29)

(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)

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, NOV 2017. (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, SEP 21 2018. (09/16150-6)

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, 2019. (14/50938-8, 09/16150-6)

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, SEP 2019. (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, MAR 2019. (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, AUG 2019. (09/16150-6, 18/23383-6)

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, 2020-02-14. (09/16150-6)

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, FEB 14 2020. (14/50938-8, 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, FEB 1 2018. (09/16150-6, 14/50938-8)

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, JUL 2016. (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, NOV 2011. (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, DEC 17 2019. (14/50938-8, 09/16150-6, 17/04377-2)

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, MAY 2021. (09/16150-6)

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, MAY 2019. (12/17657-0, 09/16150-6, 14/18103-3)

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, DEC 2020. (14/50938-8, 09/16150-6)

FERRUCCI, DANILO; BIANCARDI, MANOEL F.; NISHAN, UMAR; ROSA-RIBEIRO, RAFAELA; CARVALHO, HERNANDES F.. Desquamation takes center stage at the origin of proliferative inflammatory atrophy, epithelial-mesenchymal transition, and stromal growth in benign prostate hyperplasia. Cell Biology International, v. 41, n. 11, p. 6-pg., 2017-11-01. (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, JUN 2 2014. (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, SEP 2018. (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, JUN 2019. (09/16150-6, 18/03528-0, 09/17336-6, 10/07699-1, 15/03393-9)

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, OCT 2019. (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, FEB 2014. (08/07990-8, 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, v. 44, n. 1, p. 27-35, JAN 2020. (09/16150-6, 18/23383-6)

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, p. 19-pg., 2017-11-01. (09/16150-6)

OSORIO RODRIGUEZ, D. A.; SANTOS, A. M.; CARVALHO, H. F.; CONSONNI, S. R.. Prostatic Smooth Muscle Cells: Extracellular matrix-induced phenotypical switch.. MOLECULAR BIOLOGY OF THE CELL, v. 29, n. 26, p. 2-pg., 2018-12-15. (09/16150-6, 15/03235-4)

DELLA-COLLETA, HELOISA H. M.; CARVALHO, HERNANDES F.. Hyaluronan content and distribution in the rat ventral prostate after castration. BIOCHEMISTRY AND CELL BIOLOGY, v. 96, n. 5, p. 8-pg., 2018-10-01. (09/16150-6, 05/02601-5)

BARBOSA, G. O.; CARDOSO, A. B.; AUGUSTO, T. M.; CARVALHO, H. F.. Heparanase/Heparan Sulfate unveiled SDF-1 role on rat ventral prostate development.. MOLECULAR BIOLOGY OF THE CELL, v. 26, p. 2-pg., 2015-01-01. (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, MAR 2019. (12/17657-0, 09/16150-6)

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, FEB 20 2019. (09/16150-6)

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, NOV 28 2017. (13/07467-1, 09/16150-6)