Transcriptional Activation of the Mixed Lineage Leukemia–p27Kip1 Pathway by a Somatostatin Analogue

Horiguchi, Kazuhiko; Yamada, Masanobu; Satoh, Tetsurou; Hashimoto, Kazuhito; Hirato, Junko; Tosaka, Masahiko; Yamada, Shozo; Mori, Masataka

doi:10.1158/1078-0432.ccr-08-2473

Cited by 34 publications

(16 citation statements)

References 42 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, it has recently been shown that octreotide may interact with the Akt/mTOR pathway [6]: this raises the possibility that octreotide may inhibit HIF-dependent VEGF production, as suggested in our study by the demonstration that octreotide treatment is associated with decreased HIF intracellular levels. Several concurrent studies, using different types of endocrine and non-endocrine cells, have suggested that somatostatin and somatostatin analogues are able to inhibit PI3K and its downstream pathway [31,38,39,40]. In our study, as in previous ones [31], octreotide was found to be able to exert significant inhibitory effects on the phosphorylation of Akt, comparable to those induced by the specific PI3K inhibitor LY294002.…”

Section: Discussionsupporting

confidence: 84%

VEGF Secretion by Neuroendocrine Tumor Cells Is Inhibited by Octreotide and by Inhibitors of the PI3K/AKT/mTOR Pathway

Villaume

Blanc²,

Gouysse³

et al. 2010

Neuroendocrinology

View full text Add to dashboard Cite

Gastroenteropancreatic (GEP) endocrine tumors are hypervascular tumors able to synthesize and secrete high amounts of VEGF. We aimed to study the regulation of VEGF production in GEP endocrine tumors and to test whether some of the drugs currently used in their treatment, such as so- matostatin analogues and mTOR inhibitors, may interfere with VEGF secretion. We therefore analyzed the effects of the somatostatin analogue octreotide, the mTOR inhibitor rapamycin, the PI3K inhibitor LY294002, the MEK1 inhibitor PD98059 and the p38 inhibitor SB203850 on VEGF secretion, assessed by ELISA and Western blotting, in three murine endocrine cell lines, STC-1, INS-r3 and INS-r9. Octreotide and rapamycin induced a significant decrease in VEGF production by all three cell lines; LY294002 significantly inhibited VEGF production by STC-1 and INS-r3 only. We detected no effect of PD98059 whereas SB203850 significantly inhibited VEGF secretion in INS-r3 and INS-r9 cells only. By Western blotting analysis, we observed decreased intracellular levels of VEGF and HIF-1α under octreotide, rapamycin and LY294002. For rapamycin and LY294002, this effect was likely mediated by the inhibition of the mTOR/HIF-1/VEGF pathway. In addition to its well-known anti-secretory effects, octreotide may also act through the inhibition of the PI3K/Akt pathway, as suggested by the decrease in Akt phosphorylation detected in all three cell lines. In conclusion, our study points out to the complex regulation of VEGF synthesis and secretion in neoplastic GEP endocrine cells and suggests that the inhibition of VEGF production by octreotide and rapamycin may contribute to their therapeutic effects.

show abstract

Section: Discussionsupporting

confidence: 84%

VEGF Secretion by Neuroendocrine Tumor Cells Is Inhibited by Octreotide and by Inhibitors of the PI3K/AKT/mTOR Pathway

Villaume

Blanc²,

Gouysse³

et al. 2010

Neuroendocrinology

View full text Add to dashboard Cite

show abstract

“…In order to measure the mRNA levels of steroidogenic enzymes in each adenoma, 0.5 μL of cDNA was subjected to real-time PCR in triplicate using TaqMan probes and an Applied Biosystems 7500 sequence detection system as reported previously [25,26]. The TaqMan probes for CYP11B2 (Hs01597732_ m1), CYP11B1 (Hs01596404_m1), 17β-hydroxylase (CYP17A1) (Hs01124136_m1), cholesterol sidechain cleavage enzyme (CYP11A1) (Hs00167984_ m1), CYP21A2 (Hs00365734_g1), 3β-hydroxysteroid dehydrogenase (HSD3B2) (Hs00605123_m1), and GAPDH (Hs99999905_g1) were from Applied Biosystems.…”

Section: Real-time Rt-pcr For Steroidogenic Enzymes In Apasmentioning

confidence: 99%

Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations

et al. 2017

Self Cite

View full text Add to dashboard Cite

PRIMARY ALDOSTERONISM (PA) has been reported to affect at least 6~10% of patients with essential hypertension [1][2][3][4][5] and is caused mostly by an adrenal adenoma (aldosterone-producing adenoma, APA) or by adrenal hyperplasia (idiopathic hyperaldosteronism, IHA). Although the tumorigenesis of APA remained unclear, somatic mutations of the potassium Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations Abstract. Somatic mutations in KCNJ5 gene have been identified in patients with adrenal aldosterone-producing adenomas (APAs). We previously reported that Japanese patients with APAs had distinct characteristics from patients in Western countries; i.e. they had a high frequency of KCNJ5 mutations and exhibited a frequent association with cortisol cosecretion. Therefore, APAs among Japanese patients may have different features from those in Western countries. We added recent cases, examined 47 cases (43% male) of APAs, including clinicopathological features, KCNJ5 mutations, and the mRNA levels of several steroidogenic enzymes, and compared the results obtained to those reported in other countries. While the prevalence of KCNJ5 mutations is approximately 40% in Western countries, 37 APA cases (78.7%) showed mutations: 26 with p.G151R and 11 with p.L168R. Although a significant gender difference has been reported in the frequency of KCNJ5 mutations in Europe, we did not find any gender difference. However, the phenotypes of Japanese patients with mutations were similar to those of patients in Western countries; patients were younger and had higher plasma aldosterone levels, lower potassium levels, and higher diastolic blood pressure. Reflecting these phenotypes, APAs with mutations had higher CYP11B2 mRNA levels. However, in contrast to APAs in Western countries, Japanese APAs with mutations showed lower CYP11B1, CYP17A1, and CYP11A1 mRNA levels. These findings demonstrated that Japanese APA patients may have distinct features including a higher prevalence of KCNJ5 mutations, no gender difference in the frequency of these mutations, and characteristics similar to the zona glomerulosa.

show abstract

“…To measure the level of KCNJ5 and steroidogenic enzyme mRNA in each adenoma, 0.5 µL of cDNA was subjected to real-time PCR as reported [16,17]. All reactions were performed in triplicate using TaqMan probes and an Applied Biosystems 7500 sequence detection system.…”

Section: Expression Of Kcnj5 and Steroidogenic Enzyme Mrna Levels Detmentioning

confidence: 99%

KCNJ5 mutations in aldosterone- and cortisol-co-secreting adrenal adenomas [Rapid Communication]

et al. 2012

Self Cite

View full text Add to dashboard Cite

Transcriptional Activation of the Mixed Lineage Leukemia–p27Kip1 Pathway by a Somatostatin Analogue

Cited by 34 publications

References 42 publications

VEGF Secretion by Neuroendocrine Tumor Cells Is Inhibited by Octreotide and by Inhibitors of the PI3K/AKT/mTOR Pathway

VEGF Secretion by Neuroendocrine Tumor Cells Is Inhibited by Octreotide and by Inhibitors of the PI3K/AKT/mTOR Pathway

Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations

KCNJ5 mutations in aldosterone- and cortisol-co-secreting adrenal adenomas [Rapid Communication]

Contact Info

Product

Resources

About