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10.1158/1078-0432.CCR-12-0037

http://scihub22266oqcxt.onion/10.1158/1078-0432.CCR-12-0037
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C4582155!4582155!22733541
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suck abstract from ncbi


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pmid22733541      Clin+Cancer+Res 2012 ; 18 (16): 4313-24
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  • The zinc finger gene ZIC2 has features of an oncogene and its over- expression correlates strongly with the clinical course of epithelial ovarian cancer #MMPMID22733541
  • Marchini S; Poynor E; Barakat RR; Clivio L; Cinquini M; Fruscio R; Porcu L; Bussani C; D?Incalci M; Erba E; Romano M; Cattoretti G; Katsaros D; Koff A; Luzzatto L
  • Clin Cancer Res 2012[Aug]; 18 (16): 4313-24 PMID22733541show ga
  • Purpose: Epithelial ovarian tumors (EOTs) are amongst the most lethal of malignancies in women. We have previously identified ZIC2 as expressed at a higher level in samples of a malignant form (MAL) of EOT than in samples of a form with low malignant potential (LMP). We have now investigated the role of ZIC2 in driving tumor growth and its association with clinical outcomes. Experimental Design: ZIC2 expression levels were analysed in two independent tumor tissue collections of LMP and MAL. In vitro experiments aimed to test the role of ZIC2 as a transforming gene. Cox models were used to correlate ZIC2 expression with clinical endpoints. Results: ZIC2 expression was about 40-fold in terms of mRNA and about 17-fold in terms of protein in MAL (n = 193) versus LMP (n = 39) tumors. ZIC2 mRNA levels were high in MAL cell lines, but undetectable in LMP cell lines. Over-expression of ZIC2 was localized to the nucleus. ZIC2 over-expression increases the growth rate and foci formation of NIH 3T3 cells, and stimulates anchorage-independent colony formation; down-regulation of ZIC2 decreases the growth rate of MAL cell lines. Zinc finger domains 1 and 2 are required for transforming activity. In stage I MAL ZIC2 expression was significantly associated with overall survival in both univariate (p = 0.046), and multivariate model (p = 0.049). Conclusions: ZIC2, a transcription factor related to the sonic hedgehog pathway, is a strong discriminant between MAL and LMP tumors: it may be a major determinant of outcome of EOT.
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