Frequent mutations of <i>β‐catenin</i> gene in sporadic secreting adrenocortical adenomas*

Tadjine, Mimi; Lampron, Antoine; Ouadi, Lydia; Bourdeau, Isabelle

doi:10.1111/j.1365-2265.2007.03033.x

Cited by 116 publications

(114 citation statements)

References 28 publications

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“…In fact, it was obtained a significant dose-dependent increasing of apoptosis rate (31%), but cell viability was limited to 40% even after high doses of OSI-906. Since resistant colorectal cancer cells present upregulation of the WNT pathway (Pitts et al 2010), the mild decrease of cell viability in NCI-H295A cells could be related to the constitutive activation of Wnt/β-catenin signaling due to S45P mutation in this cell line (Tadjine et al 2008).…”

Section: Discussionmentioning

confidence: 99%

IGF2 and IGF1R in pediatric adrenocortical tumors: roles in metastasis and steroidogenesis

Lira¹,

Fedatto²,

Antônio³

et al. 2016

Endocrine-Related Cancer

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Deregulation of the IGF system observed in human tumors indicates a role in malignant cell transformation and in tumor cell proliferation. Although overexpression of the IGF2 and IGF1R genes was described in adrenocortical tumors (ACTs), few studies reported their profiles in pediatric ACTs. In this study, the IGF2 and IGF1R expression was evaluated by RT-qPCR according to the patient's clinical/pathological features in 60 pediatric ACT samples, and IGF1R protein was investigated in 45 samples by immunohistochemistry (IHC). Whole transcriptome and functional assays were conducted after IGF1R inhibition with OSI-906 in NCI-H295A cell line. Significant IGF2 overexpression was found in tumor samples when compared with non-neoplastic samples (P < 0.001), significantly higher levels of IGF1R in patients with relapse/metastasis (P = 0.031) and moderate/strong IGF1R immunostaining in 62.2% of ACTs, but no other relationship with patient survival and clinical/pathological features was observed. OSI-906 treatment downregulated genes associated with MAPK activity, induced limited reduction of cell viability and increased the apoptosis rate. After 24 h, the treatment also decreased the expression of genes related to the steroid biosynthetic process, the protein levels of the steroidogenic acute regulatory protein (STAR), and androgen secretion in cell medium, supporting the role of IGF1R in steroidogenesis of adrenocortical carcinoma cells. Our data showed that the IGF1R overexpression could be indicative of aggressive ACTs in children. However, in vitro treatments with high concentrations of OSI-906 (>1 μM) showed limited reduction of cell viability, suggesting that OSI-906 alone could not be a suitable therapy to abolish carcinoma cell growth. 23:6Research R C P Lira et al.IGF1R in pediatric adrenocortical tumor IGF2 and IGF1R in pediatric adrenocortical tumors: roles in metastasis and steroidogenesis

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Section: Discussionmentioning

confidence: 99%

IGF2 and IGF1R in pediatric adrenocortical tumors: roles in metastasis and steroidogenesis

Lira¹,

Fedatto²,

Antônio³

et al. 2016

Endocrine-Related Cancer

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“…Mutations of genes that encode G-protein subunit α, type 1α regulatory subunit of cAMP-dependent PKA, and phosphodiesterases type 11A and type 8B have also been identified in adrenocortical adenoma or hyperplasia [26][27][28][29]. Activation of the Wnt/β-catenin signaling pathway has been shown to affect adrenocortical tumorigenesis [30][31][32]. Moreover, mutations of tumor suppressor genes such as p53, MEN1 and ARMC5 have been observed in adrenocortical adenoma or hyperplasia [24,33,34].…”

Section: Discussionmentioning

confidence: 99%

Long-term study of subclinical Cushing^|^rsquo;s syndrome shows high prevalence of extra-adrenal malignancy in patients with functioning bilateral adrenal tumors

et al. 2014

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“…BMAH tissue specimens were obtained at surgery from patients II-1 and III-4 and were immediately frozen in liquid nitrogen and stored at K80 8C. Tumor DNA was extracted from frozen tissues as described previously (27).…”

Section: Patients and Adrenocortical Samplesmentioning

confidence: 99%

ARMC5 mutations in a large French-Canadian family with cortisol-secreting β-adrenergic/vasopressin responsive bilateral macronodular adrenal hyperplasia

Bourdeau

Oble²,

Magne³

et al. 2016

European Journal of Endocrinology

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Background: Bilateral macronodular adrenal hyperplasia (BMAH) is a rare cause of Cushing's syndrome (CS) and its familial clustering has been described previously. Recent studies identified that ARMC5 mutations occur frequently in BMAH, but the relation between ARMC5 mutation and the expression of aberrant G-protein-coupled receptor has not been examined in detail yet. Methods: We studied a large French-Canadian family with BMAH and sub-clinical or overt CS. Screening was performed using the 1-mg dexamethasone suppression test (DST) in 28 family members. Screening for aberrant regulation of cortisol by various hormone receptors were examined in vivo in nine individuals. Sequencing of the coding regions of ARMC5 gene was carried out. Results: Morning ambulating cortisol post 1 mg DST were O50 nmol/l in 5/8 members in generation II (57-68 years old), 9/22 in generation III (26-46 years old). Adrenal size was enlarged at different degrees. All affected patients increased cortisol following upright posture, insulin-induced hypoglycemia and/or isoproterenol infusion. b-blockers led to the reduction of cortisol secretion in all patients with the exception of two who had adrenalectomies because of b-blockers intolerance. We identified a heterozygous germline variant in the ARMC5 gene c.327_328insC, (p.Ala110Argfs*9) in nine individuals with clinical or subclinical CS, in four out of six individuals with abnormal suppression to dexamethasone at initial investigation and one out of six individuals with current normal clinical screening tests. Conclusions: Systematic screening of members of the same family with hereditary BMAH allows the diagnosis of unsuspected subclinical CS associated with early BMAH. The relation between the causative ARMC5 mutation and the reproducible pattern of aberrant b-adrenergic and V 1 -vasopressin receptors identified in this family remains to be elucidated.

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Frequent mutations of β‐catenin gene in sporadic secreting adrenocortical adenomas*

Abstract: Activating mutations of exon 3 of the beta-catenin gene are frequent in adrenocortical adenomas, and further characterization of the Wnt/beta-catenin signalling pathway should lead to a better understanding of adrenal tumourigenesis.

Cited by 116 publications

References 28 publications

IGF2 and IGF1R in pediatric adrenocortical tumors: roles in metastasis and steroidogenesis

IGF2 and IGF1R in pediatric adrenocortical tumors: roles in metastasis and steroidogenesis

Long-term study of subclinical Cushing^|^rsquo;s syndrome shows high prevalence of extra-adrenal malignancy in patients with functioning bilateral adrenal tumors

ARMC5 mutations in a large French-Canadian family with cortisol-secreting β-adrenergic/vasopressin responsive bilateral macronodular adrenal hyperplasia

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