Novel genes involved in pathophysiology of gonadotropin-dependent adrenal tumors in mice

TY - JOUR

T1 - Novel genes involved in pathophysiology of gonadotropin-dependent adrenal tumors in mice

AU - Doroszko, Milena

AU - Chrusciel, Marcin

AU - Belling, Kirstine G

AU - Vuorenoja, Susanna

AU - Dalgaard, Marlene

AU - Leffers, Henrik

AU - Nielsen, H Bjørn

AU - Huhtaniemi, Ilpo

AU - Toppari, Jorma

AU - Rahman, Nafis A

N1 - Copyright © 2017 Elsevier B.V. All rights reserved.

PY - 2017/3/15

Y1 - 2017/3/15

N2 - Specific inbred strains and transgenic inhibin-α Simian Virus 40 T antigen (inhα/Tag) mice are genetically susceptible to gonadectomy-induced adrenocortical neoplasias. We identified altered gene expression in prepubertally gonadectomized (GDX) inhα/Tag and wild-type (WT) mice. Besides earlier reported Gata4 and Lhcgr, we found up-regulated Esr1, Prlr-rs1, and down-regulated Grb10, Mmp24, Sgcd, Rerg, Gnas, Nfatc2, Gnrhr, Igf2 in inhα/Tag adrenal tumors. Sex-steroidogenic enzyme genes expression (Srd5a1, Cyp19a1) was up-regulated in tumors, but adrenal-specific steroidogenic enzyme (Cyp21a1, Cyp11b1, Cyp11b2) down-regulated. We localized novel Lhcgr transcripts in adrenal cortex parenchyma and in non-steroidogenic A cells, in GDX WT and in intact WT mice. We identified up-regulated Esr1 as a potential novel biomarker of gonadectomy-induced adrenocortical tumors in inhα/Tag mice presenting with an inverted adrenal-to-gonadal steroidogenic gene expression profile. A putative normal adrenal remodeling or tumor suppressor role of the down-regulated genes (e.g. Grb10, Rerg, Gnas, and Nfatc2) in the tumors remains to be addressed.

AB - Specific inbred strains and transgenic inhibin-α Simian Virus 40 T antigen (inhα/Tag) mice are genetically susceptible to gonadectomy-induced adrenocortical neoplasias. We identified altered gene expression in prepubertally gonadectomized (GDX) inhα/Tag and wild-type (WT) mice. Besides earlier reported Gata4 and Lhcgr, we found up-regulated Esr1, Prlr-rs1, and down-regulated Grb10, Mmp24, Sgcd, Rerg, Gnas, Nfatc2, Gnrhr, Igf2 in inhα/Tag adrenal tumors. Sex-steroidogenic enzyme genes expression (Srd5a1, Cyp19a1) was up-regulated in tumors, but adrenal-specific steroidogenic enzyme (Cyp21a1, Cyp11b1, Cyp11b2) down-regulated. We localized novel Lhcgr transcripts in adrenal cortex parenchyma and in non-steroidogenic A cells, in GDX WT and in intact WT mice. We identified up-regulated Esr1 as a potential novel biomarker of gonadectomy-induced adrenocortical tumors in inhα/Tag mice presenting with an inverted adrenal-to-gonadal steroidogenic gene expression profile. A putative normal adrenal remodeling or tumor suppressor role of the down-regulated genes (e.g. Grb10, Rerg, Gnas, and Nfatc2) in the tumors remains to be addressed.

KW - Adrenal Gland Neoplasms/genetics

KW - Animals

KW - Biomarkers, Tumor/metabolism

KW - GATA Transcription Factors/metabolism

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Neoplastic/drug effects

KW - Gene Ontology

KW - Genes, Neoplasm

KW - Gonadotropins/pharmacology

KW - Male

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Oligonucleotide Array Sequence Analysis

KW - Reproducibility of Results

KW - Steroids/biosynthesis

U2 - 10.1016/j.mce.2017.01.036

DO - 10.1016/j.mce.2017.01.036

M3 - Journal article

C2 - 28131743

SN - 0303-7207

VL - 444

SP - 9

EP - 18

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

ER -