BACKGROUND Nurr1, a member of the nuclear receptor superfamily of transcription factors, is highly expressed in midbrain dopaminergic (DA) neurons. Ret is a member of the receptor tyrosine kinase (RTK) superfamily and a critical signal transducing subunit of receptors for glial cell line-derived neurotrophic factor (GDNF). Both Nurr1 and Ret play important roles in the development of DA neurons...

CONTEXT RET/PTC rearrangements have been reported in papillary thyroid carcinomas with variable frequency in studies that used different detection methods. OBJECTIVE Our objective was to determine the role of different detection methods and tumor genetic heterogeneity on RET/PTC detection. DESIGN Sixty-five papillary carcinomas were analyzed for RET/PTC1 and RET/PTC3 using five detection me...

Persistent RET activation is a frequent event in papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC). In these cancers, RET activates the ERK/MAPK, the PI3K/AKT/mTOR and the JAK/STAT3 pathways. Here, we tested the efficacy of a JAK1/2- inhibitor, AZD1480, in the in vitro and in vivo growth of thyroid cancer cell lines expressing oncogenic RET. Thyroid cancer cell lines harbo...

The RET kinase has emerged as a promising target for the therapy of medullary thyroid cancers (MTC) and of a subset of papillary thyroid cancers. NVP-AST487, a N,N ¶-diphenyl urea with an IC50 of 0.88 Mmol/L on RET kinase, inhibited RET autophosphorylation and activation of downstream effectors, and potently inhibited the growth of human thyroid cancer cell lines with activating mutations of RE...

Rai is a recently identified member of the family of Shc-like proteins, which are cytoplasmic signal transducers characterized by the unique PTB-CH1-SH2 modular organization. Rai expression is restricted to neuronal cells and regulates in vivo the number of postmitotic sympathetic neurons. We report here that Rai is not a common substrate of receptor tyrosine kinases under physiological conditi...

Intestinal adaptation is an important compensatory response to massive small bowel resection (SBR) and occurs because of a proliferative stimulus to crypt enterocytes by poorly understood mechanisms. Recent studies suggest the enteric nervous system (ENS) influences enterocyte proliferation. We, therefore, sought to determine whether ENS dysfunction alters resection-induced adaptation responses...

PURPOSE Recent findings suggest that combination treatment with antiestrogen and anti-RET may offer a novel treatment strategy in a subset of patients with breast cancer. We investigated the role of RET in potentiating the effects of antiestrogen response and examined whether RET expression predicted the ability for tyrosine kinase inhibitor (TKI) to affect extracellular signal-regulated kinase...

Stable CTAB micelles loaded with DiI and DiD are prepared, showing RET. Remarkably, the RET efficiency increases upon diluting sample below critical micellar concentration, as dyes cluster around CTAB.

Radiation-induced human papillary thyroid cancer (PTC) is associated with chromosomal inversions that involve the genetic loci H4 and RET on chromosome 10. Recently, experimental data has shown that these loci lie in very close spatial proximity in a high proportion of adult human thyroid cells. Applying the generalized formulation of dual radiation action to this H4-to-RET geometric distance d...

The GDNF family ligands (GFLs: GDNF, neurturin, persephin, and artemin) signal through RET and a gly-cosyl-phosphatidylinositol (GPI)-anchored coreceptor (GFRalpha1-alpha4) that binds ligand with high affinity and provides specificity. The importance of the GPI anchor is not fully understood; however, GPI-linked proteins cluster into lipid rafts, structures that may represent highly specialized...