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15th International & 14th European Congress of Endocrinology

Oral Communications

Adrenal Basic

ea0029oc13.1 | Adrenal Basic | ICEECE2012

Targeting multiple signalling pathways showed high anti-tumour potential in two mouse phaeochromocytoma cell lines

Nolting S. , Garcia E. , Alusi G. , Korbonits M. , Grossman A.

Introduction: Since there is no completely effective therapy available for malignant phaeochromocytomas (PCCs) and paragangliomas, we have been investigating novel targeted therapies utilising one more benign (MPC) and one more malignant (MTT) PCC cell line. We have previously shown that the IGF1-receptor-inhibitor NVP-AEW541 led to compensatory ERK and mTORC1 up-regulation at suboptimal doses and that the dual PI3K/mTORC1-inhibitor NVP-BEZ235 also resulted in compensatory ERK...

ea0029oc13.2 | Adrenal Basic | ICEECE2012

VSNL1 is upregulated in aldosterone producing adenomas with KCNJ5 mutations and protects from calcium-induced apoptosis

Monticone S. , Crudo V. , Burrello J. , Galmozzi M. , Warth R. , Veglio F. , Mulatero P. , Williams T.

Visinin-like 1 (VSNL1) is upregulated in aldosterone-producing adenomas (APA) compared to normal adrenals. We demonstrate that VSNL1 overexpression in adrenocortical carcinoma cells (NCI H295R) upregulates basal and angiotensin II (Ang II)-stimulated CYP11B2 gene expression 3.2- and 1.5-fold, respectively. Conversely, silencing VSNL1 by RNA interference decreases Ang II-stimulated CYP11B2 expression and aldosterone secretion by 41 and 34.5%, respectively. Mutations in the pota...

ea0029oc13.3 | Adrenal Basic | ICEECE2012

Cortisol secretion is dependent on intraadrenal production of ACTH in macronodular bilateral adrenal hyperplasia causing Cushings syndrome

Louiset E. , Duparc C. , Young J. , Boutelet I. , Renouf S. , Bram Z. , Groussin L. , Caron P. , Tabarin A. , Grunenberger F. , Christin-Maitre S. , Kuhn J. , Anouar Y. , Bertherat J. , Lefebvre H.

Illicit expression of membrane receptors for circulating regulatory factors, such as gastric inhibitory polypeptide (GIP), luteinizing hormone (LH) and serotonin (5-HT) receptors, has been well documented in ACTH-independent macronodular adrenal hyperplasias (AIMAHs) causing Cushing’s syndrome. In addition, we have observed an abnormal expression of ACTH in some steroidogenic cells in two AIMAH tissues. The aim of the present study was to investigate the role of local pro...

ea0029oc13.4 | Adrenal Basic | ICEECE2012

A genome-wide methylation study of adrenocortical tumors shows specific alterations linked to gene expression, revealing new aspects of the molecular classification of adrenal carcinomas

Assie G. , Barreau O. , Wilmot-Roussel H. , Ragazzon B. , Baudry C. , Perlemoine K. , Rene-Corail F. , Dousset B. , Bertagna X. , Tissier F. , De Reynies A. , Bertherat J.

Introduction: DNA methylation is a mechanism for gene expression dysregulation in cancer. Little is known about methylation in adrenocortical tumors (ACT). Previous transcriptome studies proposed an original classification of ACT, first discriminating carcinomas from adenomas, then separating the carcinomas in two groups with different prognosis (C1A and C1B), the poor outcome group (C1A) being divided in three subgroups: p53 inactivation sub-group (C1Ap53), β-catenin act...

ea0029oc13.5 | Adrenal Basic | ICEECE2012

KCNJ5 mutations in Japanese patients with aldosterone-producing adenomas

Yamada M. , Taguchi R. , Nakajima Y. , Satoh T. , Hashimoto K. , Shibusawa N. , Ozawa A. , Tomaru T. , Okada S. , Rokutanda N. , Takata D. , Koibuchi Y. , Horiguchi J. , Oyama T. , Takeyoshi I. , Mori M.

Background: Primary aldosteronism (PA) has been reported to affect about 10% of patients with essential hypertension. In Western countries, about one third of them have aldosterone-producing adenomas (APA), and mutations of the KCNJ5 gene have recently been identified in approximately 30% of APAs. In contrast, most Japanese (~80%) with PA have APA. Therefore, Japanese PA may have different characteristics from patients in Western countries, and those with mutations of the KCNJ...

ea0029oc13.6 | Adrenal Basic | ICEECE2012

GATA-4 overexpression induces adrenocortical tumorigenesis and ectopic expression of luteinizing hormone receptor in C57Bl/6J mice

Chrusciel M. , Vuorenoja S. , Mohanty B. , Rivero-Muller A. , Lei Z. , Toppari J. , Li X. , Huhtaniemi I. , Rahman N.

We have earlier shown a reciprocal feed-forward amplification link between expression of transcription factor GATA-4 and luteinizing hormone receptor (LHR) during adrenocortical tumorigenesis, and also that chronically elevated LH levels may induce LHR in mice, but not GATA-4. Hereby, our goal was to analyze the consequences of ectopically expressed GATA-4 on murine adrenal cortex in the presence and absence of gonadectomy (GDX) induced elevated LH levels. For this purpose, we...