HNF1α inhibition triggers epithelial-mesenchymal transition in human liver cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Hepatocyte Nuclear Factor 1α (HNF1α) is an atypical homeodomain-containing transcription factor that transactivates liver-specific genes including albumin, α-1-antitrypsin and α- and β-fibrinogen. Biallelic inactivating mutations of <it>HNF1A </it>have been frequently identified in hepatocellular adenomas (HCA), rare benign liver tumors usually developed in women under oral contraceptives, and in rare cases of hepatocellular carcinomas developed in non-cirrhotic liver. HNF1α-mutated HCA (H-HCA) are characterized by a marked steatosis and show activation of glycolysis, lipogenesis, translational machinery and mTOR pathway. We studied the consequences of HNF1α silencing in hepatic cell lines, HepG2 and Hep3B and we reproduced most of the deregulations identified in H-HCA.</p> <p>Methods</p> <p>We transfected hepatoma cell lines HepG2 and Hep3B with siRNA targeting HNF1α and obtained a strong inhibition of HNF1α expression. We then looked at the phenotypic changes by microscopy and studied changes in gene expression using qRT-PCR and Western Blot.</p> <p>Results</p> <p>Hepatocytes transfected with HNF1α siRNA underwent severe phenotypic changes with loss of cell-cell contacts and development of migration structures. In HNF1α-inhibited cells, hepatocyte and epithelial markers were diminished and mesenchymal markers were over-expressed. This epithelial-mesenchymal transition (EMT) was related to the up regulation of several EMT transcription factors, in particular <it>SNAIL </it>and <it>SLUG</it>. We also found an overexpression of TGFβ1, an EMT initiator, in both cells transfected with HNF1α siRNA and H-HCA. Moreover, TGFβ1 expression is strongly correlated to HNF1α expression in cell models, suggesting regulation of TGFβ1 expression by HNF1α.</p> <p>Conclusion</p> <p>Our results suggest that HNF1α is not only important for hepatocyte differentiation, but has also a role in the maintenance of epithelial phenotype in hepatocytes.</p

Symptom validity assessment: Practice issues and medical necessity: NAN Policy & Planning Committee

Symptom exaggeration or fabrication occurs in a sizeable minority of neuropsychological examinees, with greater prevalence in forensic contexts. Adequate assessment of response validity is essential in order to maximize confidence in the results of neurocognitive and personality measures and in the diagnoses and recommendations that are based on the results. Symptom validity assessment may include specific tests, indices, and observations. The manner in which symptom validity is assessed may vary depending on context but must include a thorough examination of cultural factors. Assessment of response validity, as a component of a medically necessary evaluation, is medically necessary. When determined by the neuropsychologist to be necessary for the assessment of response validity, administration of specific symptom validity tests are also medically necessary. © 2005 Published by Elsevier Ltd on behalf of National Academy of Neuropsychology

The importance of neuropsychological assessment for the evaluation of childhood learning disorders NAN Policy and Planning Committee

When children experience learning difficulties, an appropriate evaluation of abilities and skills can provide the foundation for an accurate diagnosis and useful recommendations. When comprehensive information about a child\u27s brain-related strengths and weaknesses is necessary to understand potential sources of the problem and implications for functioning, a neuropsychological evaluation is most often the best choice. This paper was written to help parents, educators, health care providers, and third-party payors to understand the nature of neuropsychological assessment and to choose the type of evaluation that will furnish relevant information for the child\u27s educational planning