The expression of estrogen-related receptor-(ERR ) is stimulated by estrogen in selective tissues. Recently, a correlation between ERR expression and the induction of peroxisome proliferator-activated receptor-coactivator-1 (PGC-1 ) in the liver of fasting animals and in cold-stressed brown-fat tissues and skeletal muscle was shown. To explore the molecular mechanisms of ERR regulation by diverse signals, the promoter of the human ERR gene was cloned and characterized. Mutation and deletion analyses revealed that a 53 bp region containing repeated core element AGGTCA motifs of the ERR gene serves as a multi-hormone response element (MHRE) for several nuclear receptors in transient co-transfection studies of human endometrial carcinoma (HEC-1B) cells. Among the nuclear receptors tested, ERR bound to and robustly stimulated the transcription of reporters containing at least two AGGTCA motifs. Ectopic expression of PGC-1 in HEC-1B cells strongly activated the reporter containing the MHRE, presumably via the endogenous nuclear receptor binding to the element. Reducing the endogenous level of ERR by small interfering RNA, and increasing the ERR level by ectopic expression, substantially decreased and increased respectively the transactivation capability of PGC-1 . The activation function 2 domain of the ERR and the L2 and L3 motifs of PGC-1 were essential to transactivate the MHRE. Additionally, PGC-1 increases the amount of endogenous ERR bound to the MHRE region as determined by a chromatin immunoprecipitation assay. The present study demonstrates that the MHRE of the ERR gene is a target for ERR transactivation, which is enhanced by PGC-1 .
Aim:To investigate biomarkers for predicting papillary thyroid cancer outcomes.Materials & methods:The expression of biomarkers (ITGA2, SYT12 and CDH3) was studied in a prospective cohort of patients with papillary thyroid cancer. Three outcomes of initial metastases, baseline status and longitudinal status were analyzed and correlated with the biomarkers.Results:
SYT12 provided the best prediction of initial metastasis (sensitivity: 72%; specificity: 54%). SYT12 had the highest accuracy for predicting longitudinal status (sensitivity: 100%; specificity: 47%). The best performance for longitudinal status resulted from combining SYT12 with American Thyroid Association risk stratification, with sensitivity and specificity of 88 and 73%, respectively.Conclusion:
SYT12 has some prognostic significance in papillary thyroid cancer. Further validation studies in larger populations are warranted.
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