Prostate cancer: changes in the Syndecan proteoglycans, oxidative stress enzyme sulfiredoxin and cell cycle kinase MELK

• Grant number: 16/09532-3
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2016
• End date: October 31, 2018
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Sérgio Luis Felisbino
• Grantee: Sérgio Luis Felisbino
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated researchers: Flávia Karina Delella ; Flávio de Oliveira Lima

Abstract

Prostate cancer (PCa) is the second most frequent and the second highest rate of morbidity and mortality among men. Studies highlight the role of stroma in the initiation and progression of CaP, as well as oxidative stress and kinase enzymes. In a previous project with the collaboration of the University of Cambridge-UK, two strains of knockout mice, one deficient in Pten and other deficient in both p53 and pRb in prostatic epithelium, were used to generate the transcriptome of normal and tumoral prostatic lobes at different stages of progression, by next generation sequencing of RNAs. Analyses of these transcriptomes have revealed changes in the expression of hundreds of genes. In this project we will characterize in more detail, in three sub-projects (already supported by 3 FAPESP's fellowships), changes in genes related to reactive stroma, such as proteoglycans in the family sindecans 1-4 and its binding protein Syntenin; the gene related to oxidative stress of sulfiredoxin enzyme (Srxn1); and the gene of the enzyme serine / threonine kinase MELK (Maternal Embryonic Leucine zipper kinase). For this, we intend to characterize by immunohistochemistry the cellular and tissue distribution of these proteoglycans and Sulfiredoxin in different stages of human prostate tumors, the pattern of gene expression of Sulfiredoxin and MELK by normal and tumoral prostate cell lines (RWPE- 1, LNCaP and PC3) at different culture conditions and the cellular viability of PC3 cells after mRNA transcription silencing for sulfiredoxin. These results will contribute to a better understanding of the role of proteoglycan family Syndecans, Sulfiredoxin and MELK enzymes in PCa, and reveal potential therapeutic targets for CaP. (AU)

Scientific publications

(4)

(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)

SANMUKH, SWAPNIL GANESH; FELISBINO, SERGIO LUIS. Development of pipette tip gap closure migration assay (s-ARU method) for studying semi-adherent cell lines. Cytotechnology, v. 70, n. 6, p. 1685-1695, DEC 2018. (16/09532-3)

BARQUILHA, CAROLINE N.; SANTOS, NILTON J.; MONCAO, CAIO C. D.; BARBOSA, ISABELA C.; LIMA, FLAVIO O.; JUSTULIN, LUIS A.; PERTEGA-GOMES, NELMA; FELISBINO, SERGIO L.. Sulfiredoxin as a Potential Therapeutic Target for Advanced and Metastatic Prostate Cancer. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, v. 2020, JAN 20 2020. (16/09532-3, 15/26097-6, 16/25945-6)

SANTOS, NILTON JOSE; BARQUILHA, CAROLINE NASCIMENTO; BARBOSA, ISABELA CORREA; MACEDO, RODRIGO TAVARES; LIMA, FLAVIO OLIVEIRA; JUSTULIN, LUIS ANTONIO; BARBOSA, GUILHERME OLIVEIRA; CARVALHO, HERNANDES F.; FELISBINO, SERGIO LUIS. Syndecan Family Gene and Protein Expression and Their Prognostic Values for Prostate Cancer. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 16, AUG 2021. (16/09532-3, 19/19644-1, 15/26175-7)

SANMUKH, SWAPNIL GANESH; SANTOS, NILTON J.; BARQUILHA, CAROLINE NASCIMENTO; DOS SANTOS, SERGIO ALEXANDRE ALCANTARA; DURAN, BRUNO OLIVEIRA SILVA; DELELLA, FLAVIA KARINA; MOROZ, ANDREI; JUSTULIN, LUIS ANTONIO; CARVALHO, HERNANDES F.; FELISBINO, SERGIO LUIS. Exposure to Bacteriophages T4 and M13 Increases Integrin Gene Expression and Impairs Migration of Human PC-3 Prostate Cancer Cells. ANTIBIOTICS-BASEL, v. 10, n. 10, OCT 2021. (16/09532-3)