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8th European Congress of Endocrinology incorporating the British Endocrine Societies

Oral Communications

Signal transduction OC1 Novartis Oncology Young Investigator Award

ea0011oc1 | Signal transduction OC1 Novartis Oncology Young Investigator Award | ECE2006

Stress response after TIF-2 disruption: loss of grip on feedback control or adrenocortical impairment?

Patchev AV , Fischer D , Herkenham M , Götz F , Wolf SS , Gehin M , Chambon P , Patchev VK , Almeida OFX

Efficiency of glucocorticoid receptor (GR) signaling is modulated by a variety of co-activators, including the transcription intermediary factor 2 (TIF-2). Although TIF-2 has been shown to amplify GR signaling in different cellular models and contexts, its system-physiological relevance has not been comprehensively examined. The present work investigated the role of TIF-2 in GR-mediated regulation of hypothalamo-pituitary-adrenal (HPA) axis activity in mice. Experiments were d...

ea0011oc2 | Signal transduction OC1 Novartis Oncology Young Investigator Award | ECE2006

Signalling and internalisation characteristics of corticotropin-releasing hormone (CRH) receptors

Markovic D , Grammatopoulos D

Corticotropin releasing hormone (CRH), and the urocortins (UCN) play key roles in mammalian pathophysiology. Their actions are mediated through two types of G-protein coupled CRH receptors, (R1 and R2) which exhibit distinct pharmacological characteristics and determine specificity of CRH and UCN actions. Several CRH-R1 mRNA splice variants have been identified in native tissues, encoding receptor isoforms with various aminoacid inserts or deletions, termed R1β, R1c, R1d ...

ea0011oc3 | Signal transduction OC1 Novartis Oncology Young Investigator Award | ECE2006

Activation of cAMP (cAMP) binding protein (CREB) by gonadotrophin-releasing hormone (GnRH) requires calcium influx and PKC activity in gonadotroph cell lines

Jonas KC , Thompson IA , Burrin JM , Fowkes RC

The ubiquitous transcription factor, CREB, is responsible for mediating gene transcription in many endocrine tissues. Recent studies reveal that the activation of several signalling pathways can lead to the phosphorylation of CREB at Ser133, including PKC, MAPKs, CaMKs, and PI3K. In the pituitary gonadotroph, there are consensus cAMP response elements (CREs) in several of the gonadotrophin subunit promoters as well as in the GnRH receptor promoter. We have previously shown tha...

ea0011oc4 | Signal transduction OC1 Novartis Oncology Young Investigator Award | ECE2006

The role of MRAP in the functional expression of the melanocortin 2 receptor

Cooray SN , Chapple JP , Metherell LA , Cheetham ME , Clark AJL

Familial Glucocorticoid Deficiency type 2 (patients with normal MC2R) is associated with mutations in the MRAP (Melanocortin Receptor Accessory Protein) gene. In order to investigate the function of this novel single transmembrane domain protein, CHO and SKN-SH cells were transfected with MRAP-FLAG and/or MC2R-GFP constructs and imaged using confocal microscopy. Although the MC2R-GFP failed to be expressed at the cell surface when transfected alone, it was found to be expresse...

ea0011oc5 | Signal transduction OC1 Novartis Oncology Young Investigator Award | ECE2006

The overexpression Pit-1 pathway, switch on by RET, get into apoptosis fate

Cañibano Acebes CM , Vidal A , Borrello MG , Diéguez C , Alcarez CV

RET is a tyrosine-kinase receptor having a GPI-linked co-receptor or GFRα. Moreover, RET has four different ligands (GDNF, NTN, ART and PSP) with its respective co-receptor (GFRα-1,-2,-3 and 4). Pituitary cells are differentiated specialized secretory cells. Sommatotrophs are responsible for growth during infancy and puberty until achievement of the final adult height. Although genetic factors leading to somatotroph hypoplasia are well known, no much is known about t...

ea0011oc6 | Signal transduction OC1 Novartis Oncology Young Investigator Award | ECE2006

Activation of androgen membrane binding sites induce potent regression of prostate cancer cells in vitro and in vivo

Papadopoulou N , Kampa M , Gravanis A , Castanas E , Stournaras C

Recent data indicate that steroid action can be completed through genomic (late) and non-genomic (rapid) mechanisms. Non-genomic androgen effects are initiated at the membrane level and imply specific secretory and signaling mechanisms different from the classical intracellular androgen receptor activation. In previous work we have reported that androgen membrane binding sites (Ambs) are present in LNCaP human prostate cancer cells. Their activation mediates a FAK/PI3K/Cdc42/R...

ea0011oc7 | Signal transduction OC1 Novartis Oncology Young Investigator Award | ECE2006

The effect of bone marrow stem cell (BMSC) differentiation on growth hormone receptor (GHR)-associated signalling pathways

Lewis MD , Easter TE , Elford C , Ludgate ME , Evans BAJ , Rees DA , Scanlon MF

GH has diverse direct effects including the induction of lipolysis in adipocytes and mineralisation in bone. Interestingly, pluripotent mesenchymal stem cells can be isolated and cultured from adult bone marrow and induced to differentiate in vitro to both adipocytes and osteoblasts. GHR activation can be coupled to JAK2/STAT5 and the ERK (MAPK) pathway. We have therefore studied the evolution of GHR-associated cell signalling in adult rat BMSC’s during differentia...

ea0011oc8 | Signal transduction OC1 Novartis Oncology Young Investigator Award | ECE2006

Role of the calcium-calmodulin dependent kinase II in oncogenic Ras-induced proliferation

Cavallo AL , Illario M , Di Vito E , Monaco S , Fenzi G , Rossi G , Vitale M

Activation of the Ras/ERK pathway and stimulation of proliferation by integrins in thyroid cells requires CaMKII activation. To date, whether this role of CaMKII is a general mechanism or is restricted to integrin signalling is unknown. As oncogenic activation of the Ras/ERK pathway by mutated Ras, RET/PTC and Trk is frequent in papillary thyroid carcinoma (PTC), we investigated the expression and activation level of CaMKII in PTC primary culture and in stable cell lines.<...