Effects of mitotane on gene expression in the adrenocortical cell line NCI-H295R: a microarray study.

Abstract

AIM:

The adrenolytic agent mitotane is widely used in the treatment of adrenocortical cancer; however, its mechanism of action is poorly elucidated. We have studied mitotane-induced mRNA expression changes in the NCI-H295R adrenocortical cancer cell line.

MATERIALS & METHODS:

Cell viability and hormone assays were used to select the optimal mitotane concentration effectively inhibiting hormone secretion without affecting cell viability. RNA isolated from cultures treated for 48 and 72 h was subjected to Agilent 4×44K microarray platforms. Microarray results were validated by quantitative reverse-transcription PCR.

RESULTS:

Altogether, 117 significantly differentially expressed genes were detected at 48 h and 72 h (p < 0.05) in mitotane-treated samples relative to controls. Three significantly underexpressed genes involved in steroid hormone biosynthesis (HSD3B1, HSD3B2 and CYP21A2) and four significantly overexpressed genes (GDF15, ALDH1L2, TRIB3 and SERPINE2) have been validated.

CONCLUSION:

Gene-expression changes might be involved in the adrenal action of mitotane and in the inhibition of hormone secretion.

• Authors: Adrienn Zsippai, Diana Rita Szabó, Zsófia Tömböl, Peter M Szabó, Katalin Eder, Eva Pállinger, Rolf C Gaillard, Attila Patócs, Sára Tóth, András Falus, Károly Rácz, Peter Igaz
• Journal: Pharmacogenomics (Pharmacogenomics) Vol. 13 Issue 12 Pg. 1351-61 (Sep 2012) ISSN: 1744-8042 [Electronic] England
• PMID: 22966885 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Hormonal
• Hormones
• RNA, Messenger
• Mitotane

Topics

• Adrenal Cortex (drug effects)
• Adrenal Cortex Neoplasms (drug therapy, genetics)
• Antineoplastic Agents, Hormonal (pharmacology)
• Cell Line, Tumor
• Cell Survival (drug effects, genetics)
• Gene Expression (drug effects, genetics)
• Hormones (genetics)
• Humans
• Microarray Analysis (methods)
• Mitotane (pharmacology)
• RNA, Messenger (genetics)