The zinc finger gene ZIC2 has features of an oncogene and its overexpression correlates strongly with the clinical course of epithelial ovarian cancer Journal Article

   

Authors:	Marchini, S.; Poynor, E.; Barakat, R. R.; 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.
Article Title:	The zinc finger gene ZIC2 has features of an oncogene and its overexpression correlates strongly with the clinical course of epithelial ovarian cancer
Abstract:	Purpose: Epithelial ovarian tumors (EOT) are among the most lethal of malignancies in women.Wehave 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 analyzed 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. Overexpression of ZIC2 was localized to the nucleus. ZIC2 overexpression increases the growth rate and foci formation of NIH3T3 cells and stimulates anchorage-independent colony formation; downregulation of ZIC2 decreases the growth rate ofMALcell 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 EOTs. © 2012 AACR.
Keywords:	signal transduction; cancer survival; controlled study; human tissue; survival rate; unclassified drug; human cell; overall survival; promoter region; disease course; cancer growth; nonhuman; outcome assessment; genetic analysis; cell proliferation; ovarian neoplasms; animal cell; mouse; animals; mice; animal tissue; gene overexpression; gene expression; cell growth; embryo; small interfering rna; gene function; cell line, tumor; carcinogenesis; transcription factors; cell transformation, neoplastic; nuclear proteins; oncogene; correlation analysis; ovary carcinoma; down regulation; metastasis potential; tumor growth; zinc finger protein; nih 3t3 cells; gene location; neoplasms, glandular and epithelial; colony formation; zinc finger protein 1; zinc finger protein 2; zic2 gene
Journal Title:	Clinical Cancer Research
Volume:	18
Issue:	16
ISSN:	1078-0432
Publisher:	American Association for Cancer Research
Date Published:	2012-08-15
Start Page:	4313
End Page:	4324
Language:	English
DOI:	10.1158/1078-0432.ccr-12-0037
PROVIDER:	scopus
PUBMED:	22733541
PMCID:	PMC4582155
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84865100609&partnerID=40&md5=8a7477b67eca60b4619eacb0a7abb9fe
Notes:	--- - "Export Date: 4 September 2012" - "CODEN: CCREF" - "Source: Scopus"

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