PASCAL

Pax8 as a marker of Ovarian cancer Originating in the Fallopian tube

Coordinatore	THE HEALTH CORPORATION - RAMBAM    more  Organization address address: HAALIYA 8 city: HAIFA postcode: 31096 contact info Titolo: Mr. Nome: Gal Cognome: Akiri Email: send email Telefono: +972 4 7771741
Nazionalità Coordinatore	Israel [IL]
Totale costo	100˙000 €
EC contributo	100˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2013-CIG
Funding Scheme	MC-CIG
Anno di inizio	2014
Periodo (anno-mese-giorno)	2014-12-01   -   2018-11-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	THE HEALTH CORPORATION - RAMBAM  Organization address address: HAALIYA 8 city: HAIFA postcode: 31096 contact info Titolo: Mr. Nome: Gal Cognome: Akiri Email: send email Telefono: +972 4 7771741	IL (HAIFA)	coordinator	100˙000.00

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 Obiettivo del progetto (Objective)

'Epithelial ovarian cancer is a disease with grim prognosis and high-grade serous carcinoma (HGSC) is its most common subtype. Recent literature suggests that HGSC arises in the fallopian tube (FT) epithelium, rather then in the ovary, and metastasizes to the ovary early on in the process of transformation. This hypothesis is based, among other findings, on common morphologic and immunophenotypic traits between HGSC and the fallopian tube secretory epithelial cell (FTSEC). One of the shared markers between HGSC and FTSEC is the transcription factor PAX8. PAX8 is known to play a critical role in FT organogenesis and as we have shown it is highly conserved in HGSC. I propose to study the role of PAX8 in FTSEC and in HGSC, thereby establishing its role as an essential lineage marker. In Aim 1 I will investigate whether PAX8 is a critical factor in cells of the FTSEC lineage. For this purpose we will use PAX8 knock down in HGSC cell lines and immortalized FTSEC lines to reveal PAX8’s activity in benign and malignant cells. As part of this aim (Aim 1b) we will test whether BCL2 is a target gene of PAX8 and a direct mediator of PAX8’s anti apoptotic role in FTSEC and HGSC. I will then use expression profiling to suggest and validate additional mediators of PAX8’s activity, thereby defining additional serous determinants. In Aim 2 I will reveal the genomic binding locations of PAX8 in benign, non-invasive and invasive carcinomas. Towards this aim we will use our unique genetically engineered mouse model of HGSC arising from the FTSEC. We will study PAX8 as a model to ask whether a transcription factor lineage marker, which is conserved throughout transformation, preserves its DNA binding profile, its target genes and its transcriptional regulatory network. Taken together, the results generated in this study will allow better understanding of the role of PAX8 in FT transformation, and will clarify the role of a transcription factor lineage marker during transformation.'