NDLI: UGT2B15, une cible pharmacologique dans le traitement du cancer de la prostate : étude Ex vivo et mise en place de modèles In vivo

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UGT2B15, une cible pharmacologique dans le traitement du cancer de la prostate : étude Ex vivo et mise en place de modèles In vivo

Content Provider	Semantic Scholar
Author	Pâquet, Sophie
Copyright Year	2011
Abstract	Androgens control cell proliferation by activating the Androgen Receptor (AR). However, high androgen levels exposition over a long period of time favours a prostate cancer (PCa). Hormone suppression is a popular treatment, which includes anti-androgens such as Casodex. Several studies on PCa cell lines have shown that androgen homeostasis is dependent on UDP-glucuronosyltransferases (UGTs) 2B15 and 2B17. This master's project has focused, on one hand, on studying UGT2B15 and 2B17's regulation by the antihormonal molecule Casodex and, on the other hand, on validating these observations in vivo. The treatment of the AR+ PCa cell lines LNCaP and LAPC-4 with Casodex in serumcontaining medium has induced UGT2B15 and 2B17 in a doseand time-dependent, as determined on transcriptional, proteic and activity levels by Real-Time PCR, Western-Blot and glucuronidation enzymatic assays. The use of a LNCaP-derived cell line containing a shRNA against AR has revealed that UGT2B15 and 2B17 induction is AR-dependent, but that their regulation by Casodex comprised AR only in UGT2B15 case. Furthermore, two types of transgenic mice for the human UGT2B15 gene have been created using the coding portion and the first intron of the human gene, with its expression controlled by the 2.4kb proximal promoter of UGT2B15 (Tg-p2B15), resulting in a tissue-distribution similar to human, or by the prostate-specific probasin promoter (Tg-p2B15), confining the transgene expression into the prostate. The characterization of these two models is currently under studies. In conclusion, Casodex utilization demonstrates a fine regulation of UGTs by androgens, which will be studied in vivo with the new transgenic mice models.
File Format	PDF HTM / HTML
Alternate Webpage(s)	https://corpus.ulaval.ca/jspui/bitstream/20.500.11794/22856/1/28347.pdf
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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