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Antitumoral effects of 9-cis retinoic acid in adrenocortical cancer.

Szabó, Diána Rita and Baghy, Kornélia and Szabó, Péter M. and Zsippai, Adrienn and Marczell, István and Nagy, Zoltán and Varga, Vivien and Éder, Katalin and Tóth, Sára and Buzás, Edit Irén and Falus, András and Kovalszky, Ilona and Patócs, Attila Balázs and Rácz, Károly and Igaz, Péter (2013) Antitumoral effects of 9-cis retinoic acid in adrenocortical cancer. CELLULAR AND MOLECULAR LIFE SCIENCES. pp. 1-16. ISSN 1420-682X

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Abstract

The currently available medical treatment options of adrenocortical cancer (ACC) are limited. In our previous meta-analysis of adrenocortical tumor genomics data, ACC was associated with reduced retinoic acid production and retinoid X receptor-mediated signaling. Our objective has been to study the potential antitumoral effects of 9-cis retinoic acid (9-cisRA) on the ACC cell line NCI-H295R and in a xenograft model. Cell proliferation, hormone secretion, and gene expression have been studied in the NCI-H295R cell line. A complex bioinformatics approach involving pathway and network analysis has been performed. Selected genes have been validated by real-time qRT-PCR. Athymic nude mice xenografted with NCI-H295R have been used in a pilot in vivo xenograft model. 9-cisRA significantly decreased cell viability and steroid hormone secretion in a concentration- and time-dependent manner in the NCI-H295R cell line. Four major molecular pathways have been identified by the analysis of gene expression data. Ten genes have been successfully validated involved in: (1) steroid hormone secretion (HSD3B1, HSD3B2), (2) retinoic acid signaling (ABCA1, ABCG1, HMGCR), (3) cell-cycle damage (GADD45A, CCNE2, UHRF1), and the (4) immune response (MAP2K6, IL1R2). 9-cisRA appears to directly regulate the cell cycle by network analysis. 9-cisRA also reduced tumor growth in the in vivo xenograft model. In conclusion, 9-cisRA might represent a promising new candidate in the treatment of hormone-secreting adrenal tumors and adrenocortical cancer.

Item Type: Article
Subjects: R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 14 Jan 2014 08:52
Last Modified: 14 Jan 2014 08:52
URI: http://real.mtak.hu/id/eprint/8670

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