In our previous study on the tumorigenesis of human functional adrenal tumors, we observed a high frequency of K-ras point mutations in clinical specimens. Furthermore, we cloned the mutated K-ras gene from the tumors and inserted it into vectors to transfect normal bovine adrenocortical cells to express the mutated K-ras gene. The mRNA level of steroidogenic enzymes such as cholesterol sidechain cleavage enzyme (P450SCC), 17alpha-hydroxylase/17,20-lyase (P450c17), and 3beta-hydroxysteroid dehydrogenase (3betaHSD) in the mutant K-ras stably transfected cells were elevated. Cultured normal adrenocortical cells from donors and patients with adrenocortical tumors were then transfected with mutant K-ras expression plasmids constructed from human adrenal tumors. Stable transfectants grew faster than normal cells. Additionally, morphologic change was observed in the transfected cells. Moreover, when the synthesis of hormones was analyzed, the mRNA of P450SCC, P450C17, and 3betaHSD was found to have increased, and the level of cortisol was 18 to 25 times that in control cells. The increased steroid hormone production in mutant K-ras-transfected cells was reversed by lovastatin, a pharmacologic inhibitor of p21ras function. These results, combined with previous reports of steroidogenic K-ras in bovine adrenocortical cells, suggest that the K-ras oncogene is involved in steroidogenesis in human adrenocortical cells.
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http://dx.doi.org/10.1089/10445490252810285 | DOI Listing |
Redox Biol
January 2025
Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany. Electronic address:
Aldosterone-producing adenomas (APAs) are a major cause of primary aldosteronism, a common form of endocrine hypertension. Here, we demonstrate that Early Growth Response 1 (EGR1) plays a dual role in adrenal cell biology, regulating both oxidative stress and aldosterone production. Using RNA sequencing of RSL3-treated human adrenal cells and spatial transcriptomics of adrenal glands from patients with primary aldosteronism, we identify EGR1 as a key gene associated with RSL3-related oxidative stress and APAs.
View Article and Find Full Text PDFGland Surg
December 2024
Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.
Background: A right adrenal gland may present in the form of adreno-hepatic fusion (AHF), in which the adrenal cells are interspersed among the hepatocytes without septation. This rare, naturally-occurring phenomenon may be associated with preoperative misdiagnosis. We present two cases of adrenal tumor in patients with AHF that were misdiagnosed, despite thorough preoperative work-ups.
View Article and Find Full Text PDFβ-elemene has a variety of anti-inflammatory, antioxidant, and antitumor effects. Currently, the influence of β-elemene on adrenocortical carcinoma (ACC) malignant progression and action mechanism remains unclear. This research aims to explore the influence and action mechanism of β-elemene on ACC progression.
View Article and Find Full Text PDFInt J Surg Pathol
January 2025
Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
Metastasis of alveolar soft part sarcoma (ASPS) to the adrenal gland is infrequent, with only eight patients reported in the literature. Here we present an ASPS in an adolescent girl presented as a hypervascular adrenal incidentaloma along with a review of the available literature. This study aims to serve as a reference to aid in the pre-operative radiological and histopathological diagnosis of this rare entity.
View Article and Find Full Text PDFClin Transl Med
January 2025
Department of Physiology, School of Basic Medicine, Shandong Second Medical University, Weifang, China.
Background: Distant metastasis occurs in the majority of adrenocortical carcinoma (ACC), leading to an extremely poor prognosis. However, the key genes driving ACC metastasis remain unclear.
Methods: Weighted gene co-expression network analysis (WGCNA) and functional enrichment analysis were conducted to identify ACC metastasis-related genes.
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