Novel markers of gonadectomy-induced adrenocortical neoplasia in the mouse and ferret

Maximiliaan Schillebeeckx, Marjut Pihlajoki, Elisabeth Gretzinger, Wei Yang, Franziska Thol, Theresa Hiller, Ann Kathrin Löbs, Theresa Röhrig, Anja Schrade, Rebecca Cochran, Patrick Y. Jay, Markku Heikinheimo, Robi D. Mitra, David B. Wilson

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Gonadectomy (GDX) induces sex steroid-producing adrenocortical tumors in certain mouse strains and in the domestic ferret. Transcriptome analysis and DNA methylation mapping were used to identify novel genetic and epigenetic markers of GDX-induced adrenocortical neoplasia in female DBA/2J mice. Markers were validated using a combination of laser capture microdissection, quantitative RT-PCR, in situ hybridization, and immunohistochemistry. Microarray expression profiling of whole adrenal mRNA from ovariectomized vs. intact mice demonstrated selective upregulation of gonadal-like genes including Spinlw1 and Insl3 in GDX-induced adrenocortical tumors of the mouse. A complementary candidate gene approach identified Foxl2 as another gonadal-like marker expressed in GDX-induced neoplasms of the mouse and ferret. That both "male-specific" (Spinlw1) and "female-specific" (Foxl2) markers were identified is noteworthy and implies that the neoplasms exhibit mixed characteristics of male and female gonadal somatic cells. Genome-wide methylation analysis showed that two genes with hypomethylated promoters, Igfbp6 and Foxs1, are upregulated in GDX-induced adrenocortical neoplasms. These new genetic and epigenetic markers may prove useful for studies of steroidogenic cell development and for diagnostic testing.

Original languageEnglish
Pages (from-to)122-130
Number of pages9
JournalMolecular and Cellular Endocrinology
Volume399
DOIs
StatePublished - Jan 5 2015

Keywords

  • Adrenal cortex
  • Endocrine tumor
  • Gonadotropin
  • Ovariectomy
  • Steroidogenesis

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