FAF1 Gene Involvement in Pituitary Corticotroph Tumors
Matthew Nguyen1, Andrea Gutierrez Maria2, Fabio R Faucz3
1Unit on Hypothalamic and Pituitary Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, United States.
Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Metabolisme
|December 8, 2023
Summary
Two novel FAF1 gene variants were found in Cushing's disease patients, potentially impacting protein structure. However, FAF1 gene defects were not associated with pituitary tumor development in mouse models or cell studies.
Area of Science:
- Endocrinology
- Genetics
- Oncology
Background:
- Cushing's disease (CD) results from pituitary corticotroph tumors causing excess corticotropin (ACTH).
- FAF1, a pro-apoptotic protein, is linked to cancers, but its role in pituitary tumors is unstudied.
Purpose of the Study:
- Investigate the involvement of FAF1 gene variants in the pathogenesis of Cushing's disease.
- Assess the functional impact of identified FAF1 variants on pituitary tumor development.
Main Methods:
- Genetic analysis of FAF1 in Cushing's disease patients.
- In vivo studies using FAF1 knockout mice.
- In vitro experiments using AtT-20 cells to evaluate ACTH secretion and proliferation.
Main Results:
- Two potentially pathogenic FAF1 variants were identified in CD patients.
- FAF1 knockout mice showed no pituitary abnormalities or altered corticosterone levels.
- In vitro studies revealed no significant changes in cell death or POMC expression, despite predicted structural protein alterations.
Conclusions:
- Identified FAF1 variants may affect protein function/structure in CD patients.
- Current in vitro and in vivo data do not support a direct link between FAF1 defects and pituitary tumorigenesis.
- Further research is needed to elucidate the precise role of FAF1 in pituitary disorders.
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