ArticleOncogene2017
P53/Rb inhibition induces metastatic adrenocortical carcinomas in a preclinical transgenic model.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Frequent antecedent nodules and diagnostic gaps in adrenocortical carcinoma.Journal of the Endocrine Society · 2026Article
- Secreted frizzled-related proteins in angiogenesis: molecular mechanisms and clinical implications.Angiogenesis · 2025Review
- Identification of CENPM as a key gene driving adrenocortical carcinoma metastasis via physical interaction with immune checkpoint ligand FGL1.Clinical and translational medicine · 2025Article
- Innovative molecular targets for combatting metastasis in adrenocortical carcinoma.Frontiers in endocrinology · 2025Article
- Dlk1 is a novel adrenocortical stem/progenitor cell marker that predicts malignancy in adrenocortical carcinoma.bioRxiv : the preprint server for biology · 2024Article
- Advances in translational research of the rare cancer type adrenocortical carcinoma.Nature reviews. Cancer · 2023Review
- Age-related Changes in the Adrenal Cortex: Insights and Implications.Journal of the Endocrine Society · 2023Review
- FLCN-Driven Functional Adrenal Cortical Carcinoma with High Mitotic Tumor Grade: Extending the Endocrine Manifestations of Birt-Hogg-Dubé Syndrome.Endocrine pathology · 2023Article
- Preclinical Models of Adrenocortical Cancer.Cancers · 2023Review
- Loss of SUMO-specific protease 2 causes isolated glucocorticoid deficiency by blocking adrenal cortex zonal transdifferentiation in mice.Nature communications · 2022Article
- Update on Biology and Genomics of Adrenocortical Carcinomas: Rationale for Emerging Therapies.Endocrine reviews · 2022Article
- Bridging the Scientific Gaps to Identify Effective Treatments in Adrenocortical Cancer.Cancers · 2022Review
- HOX genes promote cell proliferation and are potential therapeutic targets in adrenocortical tumours.British journal of cancer · 2021Article
- Current Status and Future Targeted Therapy in Adrenocortical Cancer.Frontiers in endocrinology · 2021Review
- Immunohistochemical Analysis of the Metabolic Phenotype of Adrenal Cortical Carcinoma.Endocrine pathology · 2020Article
- Metabolic Changes in Polycystic Kidney Disease as a Potential Target for Systemic Treatment.International journal of molecular sciences · 2020Review
- Wnt/β-catenin activation cooperates with loss of p53 to cause adrenocortical carcinoma in mice.Oncogene · 2020Article
- Update on in-vivo preclinical research models in adrenocortical carcinoma.Current opinion in endocrinology, diabetes, and obesity · 2020Review
- Article
- ENST00000489707.5 Is a Preferred Alternative Splicing Variant of PTK7 in Adrenocortical Cancer and Shows Potential Prognostic Value.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adrenocortical carcinoma (ACC) is a rare cancer with poor prognosis. Pan-genomic analyses identified p53/Rb and WNT/β-catenin signaling pathways as main contributors to the disease. However, isolated β-catenin constitutive activation failed to induce malignant progression in mouse adrenocortical tumors. Therefore, there still was a need for a relevant animal model to study ACC pathogenesis and to test new therapeutic approaches. Here, we have developed a transgenic mice model with adrenocortical specific expression of SV40 large T-antigen (AdTAg mice), to test the oncogenic potential of p53/Rb inhibition in the adrenal gland. All AdTAg mice develop large adrenal carcinomas that eventually metastasize to the liver and lungs, resulting in decreased overall survival. Consistent with ACC in patients, adrenal tumors in AdTAg mice autonomously produce large amounts of glucocorticoids and spontaneously activate WNT/β-catenin signaling pathway during malignant progression. We show that this activation is associated with downregulation of secreted frizzled related proteins (Sfrp) and Znrf3 that act as inhibitors of the WNT signaling. We also show that mTORC1 pathway activation is an early event during neoplasia expansion and further demonstrate that mTORC1 pathway is activated in ACC patients. Preclinical inhibition of mTORC1 activity induces a marked reduction in tumor size, associated with induction of apoptosis and inhibition of proliferation that results in normalization of corticosterone plasma levels in AdTAg mice. Altogether, these data establish AdTAg mice as the first preclinical model for metastatic ACC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.