Recurrent Amplification of the Osmotic Stress Transcription Factor NFAT5 in Adrenocortical Carcinoma
| Autor: | C. Christofer Juhlin, Norman G. Nicolson, Taylor C. Brown, Reju Korah, Adam Stenman, Jianliang Man, Tobias Carling, Courtney E. Gibson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Regulation of gene expression Adrenocortical carcinoma Endocrinology Diabetes and Metabolism Biology and SLC5A3 medicine.disease_cause medicine.disease Molecular biology Osmotic Stress 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Osmolyte NFAT5 030220 oncology & carcinogenesis medicine Immunohistochemistry Carcinogenesis Transcription factor Gene AcademicSubjects/MED00250 Research Article |
| Zdroj: | Journal of the Endocrine Society |
| ISSN: | 2472-1972 |
| Popis: | Tumorigenesis requires mitigation of osmotic stress and the transcription factor nuclear factor of activated T cells 5 (NFAT5) coordinates this response by inducing transcellular transport of ions and osmolytes. NFAT5 modulates in vitro behavior in several cancer types, but a potential role of NFAT5 in adrenocortical carcinoma (ACC) has not been studied. A discovery cohort of 28 ACCs was selected for analysis. Coverage depth analysis of whole-exome sequencing reads assessed NFAT5 copy number alterations in 19 ACCs. Quantitative real-time PCR measured NFAT5 mRNA expression levels in 11 ACCs and 23 adrenocortical adenomas. Immunohistochemistry investigated protein expression in representative adrenal samples. The Cancer Genome Atlas database was analyzed to corroborate NFAT5 findings from the discovery cohort and to test whether NFAT5 expression correlated with ion/osmolyte channel and regulatory protein expression patterns in ACC. NFAT5 was amplified in 10 ACCs (52.6%) and clustered in the top 6% of all amplified genes. mRNA expression levels were 5-fold higher compared with adrenocortical adenomas (P |
| Databáze: | OpenAIRE |
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