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HMGA1 proteins exert their major physiological function during embryonic development and play a critical role in neoplastic transformation. Here, we show that Hand1 gene, which codes for a transcription factor crucial for differentiation of trophoblast giant cells and heart development, is upregulated in hmga1 minus embryonic stem cells. We demonstrate that HMGA1 proteins bind directly to Hand1 promoter both in vitro and in vivo and inhibit Hand1 promoter activity. We have also investigated HAND1 expression in human thyroid carcinoma cell lines and tissues, in which HMGA proteins are overexpressed, with respect to normal thyroid; an inverse correlation between HMGA1 and HAND1 expression was found in all thyroid tumor histotypes. A correlation between HAND1 gene repression and promoter hypermethylation was found in anaplastic carcinomas but not in other thyroid tumor histotypes. Therefore, we can hypothesize that HMGA1 overexpression plays a key role on HAND1 silencing in differentiated thyroid carcinomas and that promoter hypermethylation occurs in later stages of thyroid tumor progression. Finally, the restoration of the HAND1 gene expression reduces the clonogenic ability of two human thyroid carcinoma-derived cell lines, suggesting that HAND1 downregulation may have a role in the process of thyroid carcinogenesis.Oncogene (2009) 28, 876–885; doi:10.1038/onc.2008.438; published online 8 December 2008 [ABSTRACT FROM AUTHOR]

We used subtractive library screening to identify the changes that occur in gene expression during thyroid cell neoplastic transformation. Complementary DNA from normal thyroid cells (HTC 2) was subtracted from a complementary DNA library constructed from a human thyroid papillary carcinoma cell line. The library was screened for genes upregulated in human thyroid papillary carcinoma cell line cells, and several cDNA clones were isolated. One of these clones has a sirtuin core and high homology with the human silent information regulator protein family. This clone, designated "SIR-T8", was overexpressed in human thyroid carcinoma cell lines and tissues, but not in adenomas. The human SIR-T8 protein has a molecular weight of 39 kDa and is primarily located in the cytoplasm under the nuclear membrane. The SIR-T8 gene is located on chromosome 17q25-1. [ABSTRACT FROM AUTHOR]

Introduction D-aspartate (D-Asp) is an atypical amino acid that binds to and activates NMDARs. D-Asp occurs abundantly in the embryonic brain of mammals and rapidly decreases after birth, due to the activity of the enzyme D-Aspartate Oxidase (DDO). The agonistic activity of D-Asp on NMDARs and its neurodevelopmental occurrence make this D-amino acid a potential mediator for NMDAR-related alterations observed in schizophrenia. Consistently, substantial reduction of D-Asp was observed in post-mortem schizophrenia brains. Aims We evaluated the potential contribution of D-Asp as neurodevelopmental modulator of brain circuits and behaviors relevant to schizophrenia. Objectives We analyzed DDO mRNA expression in the post-mortem prefrontal cortex of schizophrenic patients. Moreover, we treated knockout mice for Ddo gene ( Ddo -/- ) with the NMDAR antagonist phencyclidine to evaluate their schizophrenia-relevant behaviors and circuits. Finally, we assessed cortico-hippocampal connectivity of these mice. Methods DDO mRNA detection was performed by quantitative PCR. Phencyclidine-induced schizophrenia-like behaviours were assessed through motor activity and prepulse inhibition paradigms. Resting-state and pharmacological fMRI were used to evaluate functional circuits and connectivity. Results DDO mRNA expression is increased in frontal samples of schizophrenic patients. In mice, the absence of Ddo gene produces a significant reduction in phencyclidine-induced motor hyper-activity and prepulse inhibition deficit. Furthermore, increased levels of D-Asp in Ddo -/- animals significantly inhibit functional circuits activated by phencyclidine, and affect the development of cortico-hippocampal connectivity networks potentially involved in schizophrenia. Conclusions Our data suggest that D-Asp, through the regulation exerted by DDO, may have a role in the pathophysiology of schizophrenia. [ABSTRACT FROM AUTHOR]

British Journal of Cancer (2002) 87, 1479–1479. doi:10.1038/sj.bjc.6600636 www.bjcancer.com© 2002 Cancer Research UK [ABSTRACT FROM AUTHOR]