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

Grant number: 16/09532-3
Support type:Regular Research Grants
Duration: November 01, 2016 - October 31, 2018
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Sérgio Luis Felisbino
Grantee:Sérgio Luis Felisbino
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Assoc. researchers:Flávia Karina Delella ; Flávio de Oliveira Lima


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
(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. Web of Science Citations: 0.

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